https://www.deplatformdisease.com/blog daily 1.0 2025-04-15 https://www.deplatformdisease.com/blog/rsv monthly 0.5 2022-11-12 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/72e4773f-cabd-4775-91f7-75d32a5f0044/Screenshot+2022-11-10+at+7.41.40+PM.png General Blog - Respiratory Syncytial Virus (RSV): A pathogen that will hopefully soon be vaccine-preventable - Make it stand out More explicit depiction of the neutralizing epitopes found on RSV F and how they depend on the conformation of the protein. Consistently, the most potent neutralization sites are found exclusively on the prefusion F whereas the least potent can be found predominantly on the postfusion conformation. Graham, Barney S (2017). Vaccine development for respiratory syncytial virus. Current Opinion in Virology, 23(), 107–112. doi:10.1016/j.coviro.2017.03.012 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/6a2d19a9-fa9e-45b3-8bb6-bd3e4567d025/Screenshot+2022-11-11+at+4.16.47+PM.png General Blog - Respiratory Syncytial Virus (RSV): A pathogen that will hopefully soon be vaccine-preventable - Make it stand out Summary of the current RSV and monoclonal antibody pipeline via PATH https://media.path.org/documents/RSV_Vaccine_and_mAb_Snapshot_September_9_2022.pdf?_gl=1*1rcndrt*_ga*MTgzOTExNzQ3OC4xNjY4MTMyMjA5*_ga_YBSE7ZKDQM*MTY2ODEzMjIwOS4xLjAuMTY2ODEzMjIwOS4wLjAuMA.. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/7294f8df-8b2a-44d5-aec2-b642dbd65335/Screenshot+2022-11-10+at+12.05.38+PM.png General Blog - Respiratory Syncytial Virus (RSV): A pathogen that will hopefully soon be vaccine-preventable - Make it stand out Summary of the major mechanisms by which RSV modulates the host immune response. F and G are key targets of the immune response but have intrinsic immunomodulatory activity. F can bind and activate TLR4; it has been proposed that the signaling induced by F through TLR4 can result in desensitization of the target cell to TLR4 signaling. Other data suggest that TLR4 signaling causes the immune response to shift towards Th2 rather than Th1 which would be needed for protection. G can bind CX3CR1 and function as a chemokine to recruit cells while simultaneously suppressing production of antiviral interferon γ. G is additionally secreted in a truncated form that can act as a decoy for antibodies. RSV N protein can disrupt formation of the immunological synapse between cytotoxic cells and infected cells, thus preventing them from arresting the infection. RSV NS1 and NS2 enhance degradation of STAT2, preventing interferon responsiveness from paracrine signaling. NS2 is also capable of binding RIG-I to impair MAVS signaling that would induce an antiviral state within the infected cell. Openshaw, P. J. M., Chiu, C., Culley, F. J., & Johansson, C. (2017). Protective and Harmful Immunity to RSV Infection. Annual Review of Immunology, 35(1), 501–532. doi:10.1146/annurev-immunol-051116-052206 Figure 1 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/5de56d0b-6820-4b25-bd77-e63b51bac297/Screenshot+2022-11-06+at+10.42.48+PM.png General Blog - Respiratory Syncytial Virus (RSV): A pathogen that will hopefully soon be vaccine-preventable - Make it stand out The Seattle Flu Study’s data for RSV shows a massive decline in the 2020-2021 season, followed by a smaller season in 2021-2022. https://seattleflu.org/pathogens https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/bfd374ed-3932-4415-a589-91ba7274c4c3/Screenshot+2022-11-06+at+10.14.08+PM.png General Blog - Respiratory Syncytial Virus (RSV): A pathogen that will hopefully soon be vaccine-preventable - Make it stand out Clinical manifestations of RSV in a cohort of hospitalized and non-hospitalized infants. Caserta MT, Qiu X, Tesini B, Wang L, Murphy A, Corbett A, Topham DJ, Falsey AR, Holden-Wiltse J, Walsh EE. Development of a Global Respiratory Severity Score for Respiratory Syncytial Virus Infection in Infants. J Infect Dis. 2017 Mar 1;215(5):750-756. doi: 10.1093/infdis/jiw624. Erratum in: J Infect Dis. 2017 Sep 15;216(6):786. PMID: 28011907; PMCID: PMC5388274. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/670d74f7-6bae-493c-8264-6a233f3dae85/Screenshot+2022-11-11+at+10.33.31+AM.png General Blog - Respiratory Syncytial Virus (RSV): A pathogen that will hopefully soon be vaccine-preventable - Make it stand out Nasal RSV IgA is more predictive of protection than serum RSV neutralizing IgG, consistent with the mucosal nature of RSV infection. Habibi, M. S., Jozwik, A., Makris, S., Dunning, J., Paras, A., DeVincenzo, J. P., … Chiu, C. (2015). Impaired Antibody-mediated Protection and Defective IgA B-Cell Memory in Experimental Infection of Adults with Respiratory Syncytial Virus. American Journal of Respiratory and Critical Care Medicine, 191(9), 1040–1049. doi:10.1164/rccm.201412-2256oc https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/16525f0e-0b23-42b9-b3bf-2cedce0d9420/Screenshot+2022-11-09+at+5.13.17+PM.png General Blog - Respiratory Syncytial Virus (RSV): A pathogen that will hopefully soon be vaccine-preventable - Make it stand out Overview of RSV’s replication cycle. Following attachment, RSV releases its genome via either a macropinosome or direct fusion at the membrane. This initiates replication within the cell and the generation of progeny virions which bud out at the apical surface of the cell. Battles, M. B., & McLellan, J. S. (2019). Respiratory syncytial virus entry and how to block it. Nature Reviews Microbiology. doi:10.1038/s41579-019-0149-x https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/02ad8459-4648-4a26-88a8-a7bdf0a43ab4/Screenshot+2022-11-11+at+10.55.49+AM.png General Blog - Respiratory Syncytial Virus (RSV): A pathogen that will hopefully soon be vaccine-preventable - Make it stand out Vaccination of mCMV expressing RSV M results in CD8 T cells that rapidly control viral load on challenge with the virus. Intranasal vaccination is superior for control of the infection than intraperitoneal immunization, attributable to the induction of CD8 TRMs in the lungs that occur only with intranasal immunization. Morabito KM, Ruckwardt TR, Redwood AJ, Moin SM, Price DA, Graham BS. Intranasal administration of RSV antigen-expressing MCMV elicits robust tissue-resident effector and effector memory CD8+ T cells in the lung. Mucosal Immunol. 2017 Mar;10(2):545-554. doi: 10.1038/mi.2016.48. Epub 2016 May 25. PMID: 27220815; PMCID: PMC5123975. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/03afe0ba-2f6c-44a0-9fd2-4b7d3eb542bf/Screenshot+2022-11-05+at+12.57.40+AM.png General Blog - Respiratory Syncytial Virus (RSV): A pathogen that will hopefully soon be vaccine-preventable - Make it stand out The results of a challenge study with an attenuated strain of RSV in 15 healthy adult volunteers. Some participants had as many as 4 reinfections with the same RSV strain over 26 months and many were reinfected 2 months apart. Hall, C. B., Walsh, E. E., Long, C. E., & Schnabel, K. C. (1991). Immunity to and Frequency of Reinfection with Respiratory Syncytial Virus. Journal of Infectious Diseases, 163(4), 693–698. doi:10.1093/infdis/163.4.693 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/f62d2bfa-5f82-410f-be99-c7a1043ace23/Screenshot+2022-11-05+at+1.04.32+AM.png General Blog - Respiratory Syncytial Virus (RSV): A pathogen that will hopefully soon be vaccine-preventable - Make it stand out RSV NET hospitalization data for the US. RSV-NET: Respiratory Syncytial Virus Hospitalization Surveillance Network, Centers for Disease Control and Prevention. WEBSITE. Accessed on 5th Nov 2022 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/89268a66-4c18-4076-9ddd-5f9583198843/Screenshot+2022-11-07+at+5.58.51+PM.png General Blog - Respiratory Syncytial Virus (RSV): A pathogen that will hopefully soon be vaccine-preventable - Make it stand out Summary of key studies examining the risk of reactive airway disease following RSV infection. A consistently increased risk is observed, but the causality of the relationship remains incompletely understood. Wu, P., & Hartert, T. V. (2011). Evidence for a causal relationship between respiratory syncytial virus infection and asthma. Expert Review of Anti-Infective Therapy, 9(9), 731–745. doi:10.1586/eri.11.92 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/e658dbdc-3b5f-4386-b188-7fcfe6e5c3e8/Screenshot+2022-11-11+at+8.52.27+PM.png General Blog - Respiratory Syncytial Virus (RSV): A pathogen that will hopefully soon be vaccine-preventable - Make it stand out DS-Cav1 is an early prefusion F stabilized RSV vaccine antigen which contains substitutions (S155C and S290C) to produce a disulfide bridge between fixed and mobile parts of F, and two cavity-filling modifications (S190F and V207L) that stabilize the preF trimer. Crank, M. C., Ruckwardt, T. J., Chen, M., Morabito, K. M., Phung, E., … Costner, P. J. (2019). A proof of concept for structure-based vaccine design targeting RSV in humans. Science, 365(6452), 505–509. doi:10.1126/science.aav9033 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/08aebe79-0133-43d4-a3fc-b4121b711725/Screenshot+2022-11-05+at+1.29.22+AM.png General Blog - Respiratory Syncytial Virus (RSV): A pathogen that will hopefully soon be vaccine-preventable - Make it stand out Messacar K, Baker RE, Park SW, Nguyen-Tran H, Cataldi JR, Grenfell B. Preparing for uncertainty: endemic paediatric viral illnesses after COVID-19 pandemic disruption. Lancet. 2022 Jul 14:S0140-6736(22)01277-6. doi: 10.1016/S0140-6736(22)01277-6. Epub ahead of print. Erratum in: Lancet. 2022 Jul 18;: PMID: 35843260; PMCID: PMC9282759. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/cb089bab-2a5a-4421-84e3-fa2dd615ad31/Screenshot+2022-11-03+at+11.38.43+AM.png General Blog - Respiratory Syncytial Virus (RSV): A pathogen that will hopefully soon be vaccine-preventable - Make it stand out The data from the Lot 100 trial showing that the vaccine was ineffective at preventing RSV and seemed to result in much more severe disease upon infection. RS = RSV; Para 1 = parainfluenza type 1 KIM, H. W., CANCHOLA, J. G., BRANDT, C. D., PYLES, G., CHANOCK, R. M., JENSEN, K., & PARROTT, R. H. (1969). RESPIRATORY SYNCYTIAL VIRUS DISEASE IN INFANTS DESPITE PRIOR ADMINISTRATION OF ANTIGENIC INACTIVATED VACCINE12. American Journal of Epidemiology, 89(4), 422–434. doi:10.1093/oxfordjournals.aje.a120955 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/c20647cb-93eb-4708-828d-0a0d9cf19dc6/Screenshot+2022-11-09+at+6.45.44+PM.png General Blog - Respiratory Syncytial Virus (RSV): A pathogen that will hopefully soon be vaccine-preventable - Make it stand out RSV infection profiles and immune responses in different demographics. Key observations include that secondary infection in adults tends to result in rapid control of viral load with short-lived symptoms (owing to extensive immune memory to the virus) with a very large early, innate response compared with the elderly and with primary infection in infants. This results in more difficulty clearing the infection in the latter groups. Infants also have far less antibody to work with initially because of an absence of prior exposure history. Openshaw, P. J. M., Chiu, C., Culley, F. J., & Johansson, C. (2017). Protective and Harmful Immunity to RSV Infection. Annual Review of Immunology, 35(1), 501–532. doi:10.1146/annurev-immunol-051116-052206 Figure 1 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/91b09bda-d9c9-4658-80cb-1bb70ea38ba8/Screenshot+2022-11-11+at+10.34.20+PM.png General Blog - Respiratory Syncytial Virus (RSV): A pathogen that will hopefully soon be vaccine-preventable - Make it stand out Summary of RSV vaccine effectiveness for Pfizer’s RSVPreF vaccine candidate showing robust and durable protection from RSV lower respiratory tract infection. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-10-19-20/03-RSV-Adults-Gurtma-508.pdf https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/ece8e6e8-4655-484f-a9e4-2aefe8fd714d/Screenshot+2022-11-11+at+11.16.33+AM.png General Blog - Respiratory Syncytial Virus (RSV): A pathogen that will hopefully soon be vaccine-preventable - Make it stand out Cytokines produced during the presymptomatic phase of RSV infection are associated with outcome: in particular, early induction of IL-17A, IL-6, and IL-1β are more likely to occur in those who retain virological control of RSV (blue) than those who develop disease (red). Habibi, M. S., Thwaites, R. S., Chang, M., Jozwik, A., Paras, A., Kirsebom, F., … Openshaw, P. J. M. (2020). Neutrophilic inflammation in the respiratory mucosa predisposes to RSV infection. Science, 370(6513), eaba9301. doi:10.1126/science.aba9301 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/02801c12-933f-4c5e-aeea-b600d937b70f/Screenshot+2022-11-03+at+2.26.35+PM.png General Blog - Respiratory Syncytial Virus (RSV): A pathogen that will hopefully soon be vaccine-preventable - Make it stand out RSV illness features change along the lifespan, with very early infection being at high risk for bronchiolitis, colds seen for most infections after that, but also potential for serious worsening of underlying asthma or COPD and severe respiratory illness in the elderly. Openshaw, P. J. M., Chiu, C., Culley, F. J., & Johansson, C. (2017). Protective and Harmful Immunity to RSV Infection. Annual Review of Immunology, 35(1), 501–532. doi:10.1146/annurev-immunol-051116-052206 Figure 1 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/e44bc305-0f2f-4494-ab4d-8b74065c3f45/Screenshot+2022-11-03+at+2.54.03+PM.png General Blog - Respiratory Syncytial Virus (RSV): A pathogen that will hopefully soon be vaccine-preventable - Make it stand out The progression of severe RSV infection into bronchiolitis and lower respiratory tract disease. Meissner, H. C. (2016). Viral Bronchiolitis in Children. New England Journal of Medicine, 374(1), 62–72. doi:10.1056/nejmra1413456 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/b4c77722-4d66-4727-9998-76c1119751a1/Screenshot+2022-11-11+at+8.32.56+PM.png General Blog - Respiratory Syncytial Virus (RSV): A pathogen that will hopefully soon be vaccine-preventable - Make it stand out An example of a prefusion stabilization strategy for RSV F wherein proline residues are introduced into key positions required for transitioning between preF and postF. The dihedral angles of the prolines are highly restricted and prevent the motions required for transition to occur. Sites of proline introduction are indicated. Proline was also shown to significantly enhance expression of the protein. Krarup, Anders; Truan, Daphné; Furmanova-Hollenstein, Polina; Bogaert, Lies; Bouchier, Pascale; Bisschop, Ilona J. M.; Widjojoatmodjo, Myra N.; Zahn, Roland; Schuitemaker, Hanneke; McLellan, Jason S.; Langedijk, Johannes P. M. (2015). A highly stable prefusion RSV F vaccine derived from structural analysis of the fusion mechanism. Nature Communications, 6(), 8143–. doi:10.1038/ncomms9143 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/9997a409-e8dc-4752-b02c-c54ac1ee2f23/Screenshot+2022-11-11+at+10.00.31+PM.png General Blog - Respiratory Syncytial Virus (RSV): A pathogen that will hopefully soon be vaccine-preventable - Make it stand out Summary of RSV vaccine effectiveness for GSK’s RSVPreF3 OA+AS01E vaccine candidate showing that the vaccine elicits robust and durable protection from severe RSV disease in older adults. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-10-19-20/02-RSV-Adults-Rizkalla-508.pdf https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/a2d26b27-6045-4087-a7c1-efc26e86cddb/Screenshot+2022-11-11+at+9.41.02+PM.png General Blog - Respiratory Syncytial Virus (RSV): A pathogen that will hopefully soon be vaccine-preventable - Make it stand out Some of the key features seen in ERD (of note though, ADE is not ERD and is not known to occur with RSV). Principally, inappropriate Th2 responses with recruitment of eosinophils, neutrophils, and immune complex deposition with resultant complement activation are implicated in RSV ERD. Su, S., Du, L. & Jiang, S. Learning from the past: development of safe and effective COVID-19 vaccines. Nat Rev Microbiol 19, 211–219 (2021). https://doi.org/10.1038/s41579-020-00462-y https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1052bcdb-9f59-4e70-89cf-f295049a0581/Screenshot+2022-11-11+at+10.43.03+AM.jpg General Blog - Respiratory Syncytial Virus (RSV): A pathogen that will hopefully soon be vaccine-preventable - Make it stand out Change in nasal RSV F antibody titers in younger vs. older adults on challenge: challenge with RSV in older adults does not result in a change to titers of either pre-F or all F proteins. Ascough S, Dayananda P, Kalyan M, Kuong SU, Gardener Z, Bergstrom E, Paterson S, Kar S, Avadhan V, Thwaites R, Sanchez Sevilla Uruchurtu A, Ruckwardt TJ, Chen M, Nair D, Derrien-Colemyn A, Graham BS, Begg M, Hessel E, Openshaw P, Chiu C. Divergent age-related humoral correlates of protection against respiratory syncytial virus infection in older and young adults: a pilot, controlled, human infection challenge model. Lancet Healthy Longev. 2022 Jun;3(6):e405-e416. doi: 10.1016/S2666-7568(22)00103-9. Epub 2022 Jun 9. PMID: 36098319. https://www.deplatformdisease.com/blog/updated-covid-19-boosters-faq monthly 0.5 2022-09-17 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/d9928bb3-704e-4c52-9c75-75ba25b37f2e/Screen+Shot+2022-09-15+at+9.45.14+AM.png General Blog - Updated COVID-19 Boosters FAQ - Make it stand out Pfizer’s mouse data supporting the updated BA.4/5 booster. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/23ebb722-a63c-44b6-a41c-9e45c8d964b4/Screen+Shot+2022-09-15+at+3.04.07+PM.png General Blog - Updated COVID-19 Boosters FAQ - Make it stand out Key point from this figure: antibody titers rise much more rapidly after dose 2 than with dose 1, starting as quickly as between days 2 and 3 after the second dose for the Pfizer/BioNTech vaccine. Note though that these are antibodies that bind spike, not necessarily those that neutralize it. Ibarrondo FJ, Hofmann C, Fulcher JA, Goodman-Meza D, Mu W, Hausner MA, Ali A, Balamurugan A, Taus E, Elliott J, Krogstad P, Tobin NH, Ferbas KG, Kitchen SG, Aldrovandi GM, Rimoin AW, Yang OO. Primary, Recall, and Decay Kinetics of SARS-CoV-2 Vaccine Antibody Responses. ACS Nano. 2021 Jun 23. doi: 10.1021/acsnano.1c03972. Epub ahead of print. PMID: 34159781. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/449bc6c5-f7e2-4c62-8bcf-1b2de2a15ca2/Screen+Shot+2022-09-15+at+12.47.18+PM.png General Blog - Updated COVID-19 Boosters FAQ - Make it stand out Vaccine effectiveness of Bnt162b2 (the Pfizer/BioNTech vaccine) and Coronavac by number of doses and age. Table 2 from McMenamin ME, Nealon J, Lin Y, Wong JY, Cheung JK, Lau EHY, Wu P, Leung GM, Cowling BJ. Vaccine effectiveness of one, two, and three doses of BNT162b2 and CoronaVac against COVID-19 in Hong Kong: a population-based observational study. Lancet Infect Dis. 2022 Jul 15:S1473-3099(22)00345-0. doi: 10.1016/S1473-3099(22)00345-0. Epub ahead of print. Erratum in: Lancet Infect Dis. 2022 Sep;22(9):e239. PMID: 35850128; PMCID: PMC9286709. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/af22e4ba-ae01-4336-b489-c33208851f2c/Screen+Shot+2022-09-15+at+3.58.24+PM.png General Blog - Updated COVID-19 Boosters FAQ - Make it stand out Antigenic maps showing the relative distance of different variants from one another based on the number of vaccine doses and immune history. BA.4/5 and BA.1 are both very far from the D614G ancestral variant, meaning the risk of imprinting is reduced. Source Post-vaccination Omicron infections induce broader immunity across antigenic space than prototype mRNA COVID-19 booster vaccination or primary infection Wei Wang, Sabrina Lusvarghi, Rahul Subramanian, Nusrat J. Epsi, Richard Wang, Emilie Goguet, Anthony C Fries, Fernando Echegaray, Russell Vassell, Si’Ana Coggins, Stephanie A. Richard, David A. Lindholm, Katrin Mende, Evan Ewers, Derek Larson, Rhonda E. Colombo, Christopher Colombo, Janet O. Joseph, Julia Rozman, Alfred Smith, Tahaniyat Lalani, Catherine Berjohn, Ryan Maves, Milissa Jones, Rupal Mody, Nikhil Huprikar, Jeffrey Livezey, David Saunders, Monique Hollis-Perry, Gregory Wang, Anuradha Ganesan, Mark P. Simons, Christopher C. Broder, David Tribble, Eric D. Laing, Brian Agan, Timothy H. Burgess, Edward Mitre, Simon D. Pollett, Leah C. Katzelnick, Carol D. Weiss bioRxiv 2022.07.05.498883; doi: https://doi.org/10.1101/2022.07.05.498883 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/cb25c00c-ace8-4850-838e-b0cb4a5007df/Screen+Shot+2022-09-15+at+10.09.37+AM.png General Blog - Updated COVID-19 Boosters FAQ - Make it stand out CDC Nowcast showing current variants circulating in the US and the proportion of cases they account for (note that Nowcast estimates from 08/27/2022 on are extrapolations from prior trends). https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/766de225-e9fd-435b-8def-1f599d233f14/Screen+Shot+2022-09-15+at+9.11.00+AM.png General Blog - Updated COVID-19 Boosters FAQ - Make it stand out CDC’s interim clinical considerations summarizing authorized or approved vaccine products in the US. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/0686265c-fdab-4563-8c1d-db514013828a/Screen+Shot+2022-09-15+at+4.23.23+PM.png General Blog - Updated COVID-19 Boosters FAQ - Make it stand out Mice given the booster on the same side (ipsi) had significantly higher avidity IgG (meaning it bound the antigen more tightly) than those given the booster on the opposite side (figure D). Source Kuraoka M, Yeh CH, Bajic G, Kotaki R, Song S, Windsor I, Harrison SC, Kelsoe G. Recall of B cell memory depends on relative locations of prime and boost immunization. Sci Immunol. 2022 May 6;7(71):eabn5311. doi: 10.1126/sciimmunol.abn5311. Epub 2022 May 6. PMID: 35522723; PMCID: PMC9169233. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/750dba71-4d67-4a0d-85b0-5574a29fbe1b/Screen+Shot+2022-09-15+at+11.32.12+AM.png General Blog - Updated COVID-19 Boosters FAQ - Make it stand out Omicron neutralizing antibody titer declines much more quickly than the overall neutralizing titer against ancestral spike when ancestral spike vaccines are used, even though the peak titer is actually not bad. Source Lyke KE, Atmar RL, Islas CD, Posavad CM, Szydlo D, Paul Chourdhury R, Deming ME, Eaton A, Jackson LA, Branche AR, El Sahly HM, Rostad CA, Martin JM, Johnston C, Rupp RE, Mulligan MJ, Brady RC, Frenck RW Jr, Bäcker M, Kottkamp AC, Babu TM, Rajakumar K, Edupuganti S, Dobrzynski D, Coler RN, Archer JI, Crandon S, Zemanek JA, Brown ER, Neuzil KM, Stephens DS, Post DJ, Nayak SU, Suthar MS, Roberts PC, Beigel JH, Montefiori DC; DMID 21-0012 Study Group. Rapid decline in vaccine-boosted neutralizing antibodies against SARS-CoV-2 Omicron variant. Cell Rep Med. 2022 Jul 19;3(7):100679. doi: 10.1016/j.xcrm.2022.100679. Epub 2022 Jun 20. PMID: 35798000; PMCID: PMC9212999. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/cd23db36-acfb-46f2-b0c2-a8c2bbe9fa8e/Screen+Shot+2022-09-15+at+3.24.32+PM.png General Blog - Updated COVID-19 Boosters FAQ - Make it stand out CDC recommendations for vaccination and Evusheld for those who are moderately or severely immunocompromised. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/174bb473-6d24-4197-939e-7032ff09f17b/Screen+Shot+2022-09-15+at+12.00.50+PM.png General Blog - Updated COVID-19 Boosters FAQ - Make it stand out Omicron-neutralizing titers in response to a BA.1 booster (mRNA-1273.214) from Moderna in humans. A key point here: at this point, the response that is most representative of what is happening in the population is actually the seropositive group’s given how many people have been infected with SARS-CoV-2. Note that for seropositive individuals, the difference in antibody titer at day 29 is about 2-fold when comparing the BA.1 booster vs. the ancestral, but it’s about 1.65-fold when looking at the seronegative group. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/81e56e0a-0f7d-4531-9278-db2d2fc94a77/Screen+Shot+2022-09-15+at+5.01.09+PM.png General Blog - Updated COVID-19 Boosters FAQ - Make it stand out Those who were infected about 1 month before their booster doses (12-44 days) had antibody levels at their pre-booster baseline or below by 60 days after the booster, whereas in those with prior infections about 200 days before (orange) and those without prior infections still tended to have significantly elevated antibody levels against all the variants. Recent SARS-CoV-2 infection abrogates antibody and B-cell responses to booster vaccination Clarisa M. Buckner, Lela Kardava, Omar El Merhebi, Sandeep R. Narpala, Leonid Serebryannyy, Bob C. Lin, Wei Wang, Xiaozhen Zhang, Felipe Lopes de Assis, Sophie E.M. Kelly, I-Ting Teng, Genevieve E. McCormack, Lauren H. Praiss, Catherine A. Seamon, M. Ali Rai, Heather Kalish, Peter D. Kwong, Michael A. Proschan, Adrian B. McDermott, Anthony S. Fauci, Tae-Wook Chun, Susan Moir medRxiv 2022.08.30.22279344; doi: https://doi.org/10.1101/2022.08.30.22279344 https://www.deplatformdisease.com/blog/lohh8sikhmo4nc2wguw1do480pd3ht monthly 0.5 2022-04-13 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/fc45f1a1-69c2-4b80-b209-568716f1e498/Screen+Shot+2022-04-11+at+1.35.26+AM.png General Blog - More Pfizer Documents and More Misinterpretations - Make it stand out There is no difference in the incidence of COVID-19 for the vaccine or placebo group in the first week following immunization with the Pfizer/BioNTech COVID-19 vaccine. N Engl J Med 2021; 385:1761-1773 DOI: 10.1056/NEJMoa2110345 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/d0085bc1-1535-48ad-bfd4-2714d5bfff02/Screen+Shot+2022-04-11+at+12.39.28+AM.png General Blog - More Pfizer Documents and More Misinterpretations - Make it stand out Clip here: https://twitter.com/Christy1Gaga/status/1510104480993497089?s=20&t=wcBCpbYhvt3sujfBa4-JXg https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/92406bb9-0966-4ab9-8ffe-ac8f9e2dc617/Screen+Shot+2022-04-11+at+1.14.12+AM.png General Blog - More Pfizer Documents and More Misinterpretations - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/c5713791-4d67-40c5-9de0-f07ee6d154ee/Screen+Shot+2022-04-12+at+10.05.47+PM.png General Blog - More Pfizer Documents and More Misinterpretations - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://www.deplatformdisease.com/blog/the-leaked-pfizer-documents-are-actually-really-boring monthly 0.5 2022-04-15 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/3260b7bd-cff1-4d94-a75d-5851b5483957/Screen+Shot+2022-03-08+at+10.21.08+PM.png General Blog - The “leaked” Pfizer documents are actually really boring - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/b7b190d6-c337-4691-88d4-d07bb3f30229/Screen+Shot+2022-03-08+at+10.19.42+PM.png General Blog - The “leaked” Pfizer documents are actually really boring - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://www.deplatformdisease.com/blog/mrna-vaccines-still-dont-reverse-transcribe-and-integrate-into-your-genome monthly 0.5 2022-03-09 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/640b0b15-a4a3-4672-b2b1-ec9e1158d7a7/huh7.PNG General Blog - mRNA vaccines… still don’t reverse transcribe and integrate into your genome - Make it stand out Even 2 major clones of the Huh7 cell line have profound genetic disparities when compared with one another and both are quite different from normal human cells. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/87e82eaa-0d07-47e7-926d-fd3f30807267/Screen+Shot+2022-02-26+at+12.02.12+AM.png General Blog - mRNA vaccines… still don’t reverse transcribe and integrate into your genome - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/27a29a03-b7fd-48ee-93a7-523ee4bd1e84/Screen+Shot+2022-02-26+at+2.10.06+AM.png General Blog - mRNA vaccines… still don’t reverse transcribe and integrate into your genome - Make it stand out Figure 3 showing the relative expression of LINE-1 across different concentrations of Bnt162b2 and over time. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/5bab66f6-a456-472d-8f81-aeb7a36f6d60/Screen+Shot+2022-02-26+at+1.25.18+AM.png General Blog - mRNA vaccines… still don’t reverse transcribe and integrate into your genome - Make it stand out Figure 1 demonstrating the sequence of Bnt162b2 and the PCR amplicon. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/f5c972ee-d26f-4ac7-b535-8dc8053091a8/Screen+Shot+2022-02-26+at+2.16.43+AM.png General Blog - mRNA vaccines… still don’t reverse transcribe and integrate into your genome - Make it stand out Figure 5 showing the presence of a DNA sequence consistent with the PCR amplicon in size when the cells are treated with Bnt162b2 but not when they are not. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/44f0f940-7b99-4034-8a79-ef43402c72c3/Screen+Shot+2022-02-26+at+12.34.37+AM.png General Blog - mRNA vaccines… still don’t reverse transcribe and integrate into your genome - Make it stand out A summary of the Central Dogma of Molecular Biology as taken from my old molecular biology notes (I am not positive what the original source of this figure is and if anyone knows I would be more than happy to provide credit). https://www.deplatformdisease.com/blog/self-proclaimed-inventor-of-mrna-vaccines-robert-malone-misrepresents-an-excellent-vaccine-study monthly 0.5 2022-02-17 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/a0bd1432-bce1-4d81-af5a-6cc9e87018f2/Screen+Shot+2022-02-16+at+10.21.34+PM.png General Blog - Self-Proclaimed inventor of mRNA vaccines, Robert Malone, misrepresents an excellent vaccine study - Make it stand out An abridged summary of key historical events in the development of lipid nanoparticles for mRNA delivery. Malone played a role in the highlighted discovery in 1989. He was not responsible for nucleoside modification of mRNA (2005) which is central to the effectiveness of mRNA vaccines currently available for COVID-19 and was not involved in the projects that gave rise to either the Pfizer/BioNTech or Moderna/NIH vaccines. Figure 1 from Hou, X., Zaks, T., Langer, R., & Dong, Y. (2021). Lipid nanoparticles for mRNA delivery. Nature Reviews Materials. doi:10.1038/s41578-021-00358-0 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/70bc2dfd-8b68-40c7-85d1-ce9a526c2ee2/Screen+Shot+2022-02-17+at+1.01.38+AM.png General Blog - Self-Proclaimed inventor of mRNA vaccines, Robert Malone, misrepresents an excellent vaccine study - Make it stand out Laidlaw, B.J., Ellebedy, A.H. The germinal centre B cell response to SARS-CoV-2. Nat Rev Immunol 22, 7–18 (2022). https://doi.org/10.1038/s41577-021-00657-1 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/2a9186cc-0ed9-412c-8bdd-4e3772b98473/Screen+Shot+2022-02-17+at+12.54.35+AM.png General Blog - Self-Proclaimed inventor of mRNA vaccines, Robert Malone, misrepresents an excellent vaccine study - Make it stand out The nucleoside modification in mRNA vaccines is key to their efficacy and effectiveness. N Engl J Med 2021; 385:1436-1438 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/bf126132-2950-4f51-a0f7-1af9c2dbc1e2/Screen+Shot+2022-02-16+at+10.53.35+PM.png General Blog - Self-Proclaimed inventor of mRNA vaccines, Robert Malone, misrepresents an excellent vaccine study - Make it stand out Graphical Abstract from Röltgen et al., Immune imprinting, breadth of variant recognition, and germinal center response in human SARS-CoV-2 infection and vaccination, Cell (2022), https://doi.org/10.1016/j.cell.2022.01.018 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/21384978-b678-4968-8712-75b340a842f1/Screen+Shot+2022-02-16+at+11.22.52+PM.png General Blog - Self-Proclaimed inventor of mRNA vaccines, Robert Malone, misrepresents an excellent vaccine study - Make it stand out Key properties of B-lineage cells via Figure 10.9 from Murphy K, Weaver C. Janeway’s Immunobiology. 9th ed. Boca Raton, FL: CRC Press; 2016 Initially in the course of an immune response, there is a burst of antibodies made from plasmablasts and short-lived plasma cells. The short-lived plasma cells, as their name implies, die. This results in a decline in antibody levels. A minority of cells may go on to become long-lived plasma cells. Mainly, these cells populate the bone marrow in survival niches where they receive support from a number of other cells of the immune system, but they have also been noted to survive for decades in mucosal tissues like the gut. Memory B cells can be rapidly recalled upon encountering an antigen to differentiate into antibody-secreting cells, including long-lived plasma cells, to clear infectious threats upon a re-encounter. However, unlike the plasma cells, memory B cells can adapt to give rise to clones that cover new viral variants that may have emerged since the last encounter. This forms a second wall of immunity that works in concert with constant antibody production to protect the host. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/10d7872a-d197-47fb-a56b-a5720145ee05/Screen+Shot+2022-02-17+at+12.44.45+AM.png General Blog - Self-Proclaimed inventor of mRNA vaccines, Robert Malone, misrepresents an excellent vaccine study - Make it stand out The cyclic re-entry model describes how we develop high affinity antibodies. See text for summary. Figure 10.11 from Murphy K, Weaver C. Janeway’s Immunobiology. 9th ed. Boca Raton, FL: CRC Press; 2016 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/9c40e492-2d62-44bf-8176-b2e0a6ee52f3/Screen+Shot+2022-02-17+at+12.42.23+AM.png General Blog - Self-Proclaimed inventor of mRNA vaccines, Robert Malone, misrepresents an excellent vaccine study - Make it stand out There is no appreciable difference in the lifetime of mRNA based on nucleoside modifications. Figure S3b Parr, Callum J C; Wada, Shunsuke; Kotake, Kenjiro; Kameda, Shigetoshi; Matsuura, Satoshi; Sakashita, Souhei; Park, Soyoung; Sugiyama, Hiroshi; Kuang, Yi; Saito, Hirohide (2020). N 1-Methylpseudouridine substitution enhances the performance of synthetic mRNA switches in cells. Nucleic Acids Research, (), gkaa070–. doi:10.1093/nar/gkaa070 https://www.deplatformdisease.com/blog/the-omicron-variant-a-summary-of-what-we-know-so-far-with-a-focus-on-what-we-dont monthly 0.5 2021-12-02 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/86c5c66b-4468-4a11-abd2-5f82c620988d/Screen+Shot+2021-11-30+at+1.02.01+PM.png General Blog - The Omicron Variant: a summary of what we know so far (with a focus on what we don’t) - Make it stand out Via Genomic surveillance of SARS-CoV-2 in Belgium Report of the National Reference Laboratory (UZ Leuven & KU Leuven) Situation update – 26 of November 2021 B.1.1.529 = Omicron, the red one https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/34dda35b-8f66-4f76-9edb-85e70cc09ea1/Screen+Shot+2021-11-30+at+1.26.09+PM.png General Blog - The Omicron Variant: a summary of what we know so far (with a focus on what we don’t) - Make it stand out A labeled Omicron spike protein showing all the different amino acid changes in the spike protein. Changes with documented phenotypic effects from literature are colored light orange or cyan for insertions/deletions while others without documented phenotypic effects are colored in green. Via GISAID. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/500dbfff-63af-4d4f-96cc-08a3031c66e5/Screen+Shot+2021-11-30+at+1.03.15+PM.png General Blog - The Omicron Variant: a summary of what we know so far (with a focus on what we don’t) - Make it stand out Image via Trevor A Branch on twitter: https://twitter.com/TrevorABranch/status/1465200215275704325?s=20 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/249778c4-7491-4207-b7fd-9ccf4de2be65/Screen+Shot+2021-11-30+at+1.58.04+PM.png General Blog - The Omicron Variant: a summary of what we know so far (with a focus on what we don’t) - Make it stand out The epitope coverage of B cells tends to be concentrated at parts of the spike protein that are important in binding to ACE2 (and those that are not shielded by sugars it picks up from infecting our cells). T cells do not have such a restriction and can target almost the entire spike protein as a result. Source: https://www.medrxiv.org/content/10.1101/2021.07.01.21259833v1.full.pdf https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/7afe1c05-4fe2-4b5b-ae0e-6a7f6e02a52c/Screen+Shot+2021-11-30+at+12.22.03+PM.png General Blog - The Omicron Variant: a summary of what we know so far (with a focus on what we don’t) - Make it stand out This was a slide shared by South Africa’s CDC in a presentation here. https://www.deplatformdisease.com/blog/tromethamine-in-the-pfizer-vaccine-has-nothing-to-do-with-heart-attacks monthly 0.5 2021-11-04 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/ad234173-8b77-4d7c-9cdc-55230cc96e0a/Screen+Shot+2021-11-03+at+9.02.23+PM.png General Blog - Tromethamine in the Pfizer/BioNTech COVID-19 Vaccine has nothing to do with heart attacks - Make it stand out A screenshot containing misinformation alleging that tromethamine in the Pfizer vaccine is dangerous and also used to treat heart attacks. Essentially no part of this is accurate, as I explain shortly. https://www.deplatformdisease.com/blog/pfizer-covid-19-vaccine-for-children-aged-5-11-vrbpac-meeting-summary-and-mythbusting monthly 0.5 2021-10-29 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1635299942697-0VXROA4AJLGJ1R9L34D4/Screen+Shot+2021-10-26+at+9.58.59+PM.png General Blog - Pfizer COVID-19 Vaccine for Children Aged 5-11: VRBPAC Meeting Summary and Mythbusting - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1635298293675-HJ6WZYIV0VB55RLLF0RA/Screen+Shot+2021-10-26+at+9.31.28+PM.png General Blog - Pfizer COVID-19 Vaccine for Children Aged 5-11: VRBPAC Meeting Summary and Mythbusting - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1635300070696-PFN4AX6AR270Y7JMKBUR/Screen+Shot+2021-10-26+at+10.01.06+PM.png General Blog - Pfizer COVID-19 Vaccine for Children Aged 5-11: VRBPAC Meeting Summary and Mythbusting - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://www.deplatformdisease.com/blog/covid-19-vaccine-passport monthly 0.5 2021-09-26 https://www.deplatformdisease.com/blog/true-facts-about-antibodies monthly 0.5 2021-09-03 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1630675260234-2UX39LRUCDD8WN0FC2WK/Screen+Shot+2021-09-03+at+9.20.57+AM.png General Blog - True Facts about Antibodies - Make it stand out Murphy K, Weaver C. Janeway’s Immunobiology. 9th ed. Boca Raton, FL: CRC Press; 2016. Figure 5.20 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1630672341416-MGWJUS0KYKW6S8SI759B/Screen+Shot+2021-09-03+at+8.32.17+AM.png General Blog - True Facts about Antibodies - Make it stand out Society for Mucosal Immunology. Principles of mucosal immunology. (CRC Press, 2020) figure 11.2 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1630675585506-68AGIWB16X75A2ZVIFWK/Screen+Shot+2021-09-03+at+8.42.45+AM.png General Blog - True Facts about Antibodies - Make it stand out Lu, L., Suscovich, T., Fortune, S. et al. Beyond binding: antibody effector functions in infectious diseases. Nat Rev Immunol 18, 46–61 (2018). https://doi.org/10.1038/nri.2017.106 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1630672488714-QEKZF24A5WFQNVIRT3VM/Screen+Shot+2021-09-03+at+8.34.45+AM.png General Blog - True Facts about Antibodies - Make it stand out Murphy K, Weaver C. Janeway’s Immunobiology. 9th ed. Boca Raton, FL: CRC Press; 2016. Figure 12.12 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1630673131444-8XYOIDV81UC4Q9CDGUV5/Screen+Shot+2021-09-03+at+8.45.28+AM.png General Blog - True Facts about Antibodies - Make it stand out Lu, L., Suscovich, T., Fortune, S. et al. Beyond binding: antibody effector functions in infectious diseases. Nat Rev Immunol 18, 46–61 (2018). https://doi.org/10.1038/nri.2017.106 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1630672714895-8YPGFZPF2RGIF19WJ2CI/Screen+Shot+2021-09-03+at+8.38.18+AM.png General Blog - True Facts about Antibodies - Make it stand out Roopenian, D., Akilesh, S. FcRn: the neonatal Fc receptor comes of age. Nat Rev Immunol 7, 715–725 (2007). https://doi.org/10.1038/nri2155 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1630672212401-7HGS7BLLEH4BX86A95X7/Screen+Shot+2021-09-03+at+8.30.09+AM.png General Blog - True Facts about Antibodies - Make it stand out Rich R. Clinical immunology. 5th ed. Elsevier; 2019 Figure 4.2 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1630672281605-9EKIOK4V06PTG9IY7MXS/Screen+Shot+2021-09-03+at+8.31.08+AM.png General Blog - True Facts about Antibodies - Make it stand out Lu, L., Suscovich, T., Fortune, S. et al. Beyond binding: antibody effector functions in infectious diseases. Nat Rev Immunol 18, 46–61 (2018). https://doi.org/10.1038/nri.2017.106 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1630672605833-1PQXRFXDY3MGVZBNSA6B/Screen+Shot+2021-09-03+at+8.36.29+AM.png General Blog - True Facts about Antibodies - Make it stand out Murphy K, Weaver C. Janeway’s Immunobiology. 9th ed. Boca Raton, FL: CRC Press; 2016. Table 10.27 https://www.deplatformdisease.com/blog/8n1jrpo8moi20b4lzoi0fkpfr3udgc monthly 0.5 2021-09-09 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1630532825553-1MSR7QG8APO2QNCNT3PJ/Screen+Shot+2021-09-01+at+5.47.02+PM.png General Blog - Addressing Dr. Christina Parks’s Claims - Make it stand out The structure of various IgA antibodies. Secretory IgA is shown in panel f, defined by the presence of a secretory component, J chain, and dimeric structure. Secretory IgA must be produced locally at the site of the mucosa, and cannot enter mucosal sites from the bloodstream. Figure 11.1 from Society for Mucosal Immunology. Principles of mucosal immunology. (CRC Press, 2020). https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1630465773344-S7JAWG220EM4ZNOBQBNK/Screen+Shot+2021-08-31+at+11.09.30+PM.png General Blog - Addressing Dr. Christina Parks’s Claims - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1630605096589-CNE84GGWRO9FIVN6H0VZ/Screen+Shot+2021-09-02+at+1.51.33+PM.png General Blog - Addressing Dr. Christina Parks’s Claims - Make it stand out Vaccinated individuals who have breakthrough cases (predominantly due to the delta variant in this study) are less likely to have culture-positive virus. Shamier, M. C. et al. Virological characteristics of SARS-CoV-2 vaccine breakthrough infections in health care workers. medRxiv 2021.08.20.21262158 (2021) doi:10.1101/2021.08.20.21262158. https://www.deplatformdisease.com/blog/covid-19-vaccines-are-not-gene-therapy monthly 0.5 2021-08-29 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1630218141658-AK07U9T84CNWQJTHB41P/Screen+Shot+2021-08-29+at+2.22.18+AM.png General Blog - COVID-19 Vaccines Are NOT Gene Therapy - Make it stand out Key concepts for gene therapy. Gene therapy aims to (a) replace the function of a defective gene with a functional one, (b) suppress a pathologic genetic variant, or (c) repair a defective gene directly through genome editing. Anguela, X. M. & High, K. A. Entering the modern era of gene therapy. Annu. Rev. Med. 70, 273–288 (2019). Figure 2 https://www.deplatformdisease.com/blog/antibody-dependent-enhancement-and-covid-19-still-no-evidence monthly 0.5 2021-08-16 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1629128574480-0HA5L4UE41584TKOFHC0/Screen+Shot+2021-08-16+at+11.42.49+AM.png General Blog - Antibody-Dependent Enhancement and COVID-19: Still No Evidence - Make it stand out Global prevalence of the Kappa variant via outbreak.info https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1629128648637-QN8EB7XVLSX3T4UGZBIX/Screen+Shot+2021-08-16+at+11.44.04+AM.png General Blog - Antibody-Dependent Enhancement and COVID-19: Still No Evidence - Make it stand out Global prevalence of the Delta variant via outbreak.info. https://www.deplatformdisease.com/blog/addressing-dr-daniel-stock-claims monthly 0.5 2021-08-12 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1628557098577-YPBT7UPPN3WKL2T76BX3/Screen+Shot+2021-08-09+at+8.58.12+PM.png General Blog - Addressing Dr. Daniel Stock’s Claims - Make it stand out This is not the portrait of an ineffective vaccine. At this point approximately half of the US population is vaccinated. Using these numbers, an 8-fold reduction in the risk of symptomatic infection corresponds to approximately 88% vaccine effectiveness against symptomatic COVID. The 25-fold reduction in hospitalization and death each corresponds to 96% effectiveness. Note that this data goes up to July 24, 2021- well into the time period at which the delta variant had attained high prevalence. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1628554881240-K72ADPXWNT09XKG0DOER/Screen+Shot+2021-08-09+at+8.21.16+PM.png General Blog - Addressing Dr. Daniel Stock’s Claims - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1628555496821-PV31QISOSVEE4V0OEIIX/Screen+Shot+2021-08-09+at+8.31.31+PM.png General Blog - Addressing Dr. Daniel Stock’s Claims - Make it stand out A visual aid to explain how masks work. Source https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1628555708975-JYD73R6UJT3FHSDUIPO5/Screen+Shot+2021-08-09+at+8.34.27+PM.png General Blog - Addressing Dr. Daniel Stock’s Claims - Make it stand out The seasonality of various respiratory viruses. Source https://www.deplatformdisease.com/blog/covid-19-vaccine-acquired-vs-disease-acquired-immunity-which-is-better monthly 0.5 2021-07-29 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1627184290661-FM7J1SW413PM6JZSTB8I/Screen+Shot+2021-07-24+at+11.38.07+PM.png General Blog - COVID-19 Vaccine-Acquired vs. Disease-Acquired Immunity: Which is Better? - Make it stand out Nelson, K. E. & Williams, C. Infectious disease epidemiology. (Jones and Bartlett, 2013). https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1627255369744-3Z9FKIZI2H1O1FPYAMPI/Screen+Shot+2021-07-25+at+7.22.46+PM.png General Blog - COVID-19 Vaccine-Acquired vs. Disease-Acquired Immunity: Which is Better? - Make it stand out Khoury, D. S. et al. Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection. Nat. Med. 27, 1205–1211 (2021). https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1627105152365-SXZUMLWVI1OMPZAJZ63L/Screen+Shot+2021-07-24+at+1.39.05+AM.png General Blog - COVID-19 Vaccine-Acquired vs. Disease-Acquired Immunity: Which is Better? - Make it stand out Hartenian, E. et al. The molecular virology of coronaviruses. J. Biol. Chem. 295, 12910–12934 (2020). https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1627251706835-B222XMX9RIKYLX0W93Z2/Screen+Shot+2021-07-25+at+6.21.43+PM.png General Blog - COVID-19 Vaccine-Acquired vs. Disease-Acquired Immunity: Which is Better? - Make it stand out Crotty, S. Hybrid immunity. Science 372, 1392–1393 (2021). https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1627249547407-NW4I71W9YWB6GLYQAJCD/Screen+Shot+2021-07-25+at+5.45.42+PM.png General Blog - COVID-19 Vaccine-Acquired vs. Disease-Acquired Immunity: Which is Better? - Make it stand out Nalbandian, A. et al. Post-acute COVID-19 syndrome. Nat. Med. 27, 601–615 (2021). https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1627067769709-YO6PBET62H5IX2T164SM/Screen+Shot+2021-07-23+at+3.16.07+PM.png General Blog - COVID-19 Vaccine-Acquired vs. Disease-Acquired Immunity: Which is Better? - Make it stand out Kaufmann, S. H. E., Rouse, B. T. & Sacks, D. L. The immune response to infection. (American Society for Microbiology, 2010). https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1627062256064-0STXAN2ODF85SML9TJ2E/Screen+Shot+2021-07-23+at+1.44.12+PM.png General Blog - COVID-19 Vaccine-Acquired vs. Disease-Acquired Immunity: Which is Better? - Make it stand out Yewdell, J. W. (2021). Individuals cannot rely on COVID-19 herd immunity: Durable immunity to viral disease is limited to viruses with obligate viremic spread. PLoS Pathogens, 17(4), e1009509. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1627316293059-YK80NS7JVJHYXH5UBQH0/Screen+Shot+2021-07-26+at+12.18.07+PM.png General Blog - COVID-19 Vaccine-Acquired vs. Disease-Acquired Immunity: Which is Better? - Make it stand out Polack, F. P. et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N. Engl. J. Med. 383, 2603–2615 (2020). https://www.deplatformdisease.com/blog/myocarditis-and-covid-19-mrna-vaccines monthly 0.5 2021-07-11 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1625507219003-VDCODOOV9N6SIJ8E6ZCL/Screen+Shot+2021-07-05+at+1.46.53+PM.png General Blog - Myocarditis and COVID-19 mRNA vaccines - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1625018816158-AL17CET4SH6JGBV3RZZ5/Screen+Shot+2021-06-17+at+1.14.10+AM.png General Blog - Myocarditis and COVID-19 mRNA vaccines - Make it stand out Bennett JE, Dolin R, Blaser MJ. Mandell, Douglas, and bennett’s principles and practice of infectious diseases: 2-Volume set. 9th ed. Philadelphia, PA: Elsevier - Health Sciences Division; 2019 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1625514666564-EV7L30P7TAWFAWLRT9RN/Screen+Shot+2021-07-05+at+3.50.23+PM.png General Blog - Myocarditis and COVID-19 mRNA vaccines - Make it stand out Caforio ALP, editor. Myocarditis: Pathogenesis, Diagnosis and Treatment. 1st ed. Cham, Switzerland: Springer Nature; 2020 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1625514643859-RVTKI86P7ZHZ1O9BDKIM/Screen+Shot+2021-07-05+at+3.50.17+PM.png General Blog - Myocarditis and COVID-19 mRNA vaccines - Make it stand out Caforio ALP, editor. Myocarditis: Pathogenesis, Diagnosis and Treatment. 1st ed. Cham, Switzerland: Springer Nature; 2020 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1625275392705-SLBB3XF6QXTCHX62QNV1/Screen+Shot+2021-07-02+at+9.23.09+PM.png General Blog - Myocarditis and COVID-19 mRNA vaccines - Make it stand out Foerster SR, Canter CE, Cinar A, et al. Ventricular remodeling and survival are more favorable for myocarditis than for idiopathic dilated cardiomyopathy in childhood: an outcomes study from the Pediatric Cardiomyopathy Registry. Circ Heart Fail 2010;3(6):689–97. Figure 2A https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1624830572430-MG39DGK05WDDQTBS6G63/Screen+Shot+2021-06-27+at+5.49.27+PM.png General Blog - Myocarditis and COVID-19 mRNA vaccines - Make it stand out Wu M-H, Wu E-T, Wang C-C, et al. Contemporary postnatal incidence of acquiring acute myocarditis by age 15 years and the outcomes from a nationwide birth cohort. Pediatr Crit Care Med 2017;18(12):1153–8 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1625247835997-OK2IXNYV0WEPDFXEP7BC/Screen+Shot+2021-07-02+at+1.43.52+PM.png General Blog - Myocarditis and COVID-19 mRNA vaccines - Make it stand out Ferreira VM, Schulz-Menger J, Holmvang G, et al. Cardiovascular magnetic resonance in nonischemic myocardial inflammation: Expert recommendations. J Am Coll Cardiol 2018;72(24):3158–76 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1625018837189-6TBROV7U7PU7G6074W36/Screen+Shot+2021-06-29+at+10.07.10+PM.png General Blog - Myocarditis and COVID-19 mRNA vaccines - Make it stand out Bennett JE, Dolin R, Blaser MJ. Mandell, Douglas, and bennett’s principles and practice of infectious diseases: 2-Volume set. 9th ed. Philadelphia, PA: Elsevier - Health Sciences Division; 2019 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1623968996463-M3D5VAY3NJ6TP17IQK81/Screen+Shot+2021-06-17+at+6.29.53+PM.png General Blog - Myocarditis and COVID-19 mRNA vaccines - Make it stand out Heymans S, Eriksson U, Lehtonen J, et al. The quest for new approaches in myocarditis and inflammatory cardiomyopathy. J. Am. Coll. Cardiol. 2016;68(21):2348–2364 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1625247395537-04MCQSGGA9KV3WLBS48F/Screen+Shot+2021-07-02+at+1.36.32+PM.png General Blog - Myocarditis and COVID-19 mRNA vaccines - Make it stand out Ferreira VM, Schulz-Menger J, Holmvang G, et al. Cardiovascular magnetic resonance in nonischemic myocardial inflammation: Expert recommendations. J Am Coll Cardiol 2018;72(24):3158–76 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1625351373917-JOFTXLULUTQI9DWY2Q8A/Screen+Shot+2021-07-03+at+6.29.27+PM.png General Blog - Myocarditis and COVID-19 mRNA vaccines - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1625270245558-6JM8CI4RW1VIO1OPMCQN/Screen+Shot+2021-07-02+at+7.57.20+PM.png General Blog - Myocarditis and COVID-19 mRNA vaccines - Make it stand out Kytö V, Sipilä J, Rautava P. The effects of gender and age on occurrence of clinically suspected myocarditis in adulthood. Heart 2013;99(22):1681–4. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1625201544931-8OPA2PS7RDN0OHDSI83U/E4k7H7eXoAE9G7H.jpeg General Blog - Myocarditis and COVID-19 mRNA vaccines - Make it stand out ACIP’s most recent recommendations regarding myocarditis and the mRNA vaccine. The last one regarding a reaction following the first dose has been met with some considerable opposition from clinicians but I am puzzled as to why this is. The recommendation is very soft and emphasizes shared decision-making. There are conditions in which the risk of COVID-19 may be so great that the potential benefits of that second dose exceed the potential risks. That isn’t going to apply to most people but the option is left open for the minority who do, and similarly the choice not to get the second dose is also left open with appropriate discussion. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1624419064930-JYBPRAER1TW13AYLSZG1/Screen+Shot+2021-06-22+at+11.31.02+PM.png General Blog - Myocarditis and COVID-19 mRNA vaccines - Make it stand out Ong S, Rose NR, Čiháková D. Natural killer cells in inflammatory heart disease. Clinical Immunology. 2017;175:26–33. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1624423913090-3GD2HQ2B53AI8XCXVMER/Screen+Shot+2021-06-23+at+12.51.49+AM.png General Blog - Myocarditis and COVID-19 mRNA vaccines - Make it stand out Tschöpe C, Ammirati E, Bozkurt B, et al. Myocarditis and inflammatory cardiomyopathy: current evidence and future directions. Nat. Rev. Cardiol. 2021;18(3):169–193. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1624401269422-CXERIP97CY30D4PFUGXQ/Screen+Shot+2021-06-22+at+6.43.02+AM.png General Blog - Myocarditis and COVID-19 mRNA vaccines - Make it stand out In a mouse model of CVB3 myocarditis, there is a stereotyped sequence of cytokines which results in progression from viral to autoimmune myocarditis and then to DCM. Broadly, there is initially inflammasome activation and release of TNF-α, which is followed by type 2 inflammation as a compensatory response. Eosinophilic infiltration may follow and there is downregulation of the immunoregulatory cytokine IL-10. As the autoimmune myocarditis progresses, there is a shift to type 17-driven inflammation that causes progression to DCM. IL-17A is required for progression to DCM. Rose NR. Critical cytokine pathways to cardiac inflammation. J. Interferon Cytokine Res. 2011;31(10):705–710 This resource is strongly recommended for anyone interested in the cytokine pathways driving myocarditis and its various phases. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1624554801277-Z14IESWXQ9HF1L2SCR7J/Screen+Shot+2021-06-24+at+1.13.18+PM.png General Blog - Myocarditis and COVID-19 mRNA vaccines - Make it stand out Peretto G, Sala S, Rizzo S, et al. Arrhythmias in myocarditis: State of the art. Heart Rhythm. 2019;16(5):793–801 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1623996169428-I0VQBEX4FBK66P4YRW6V/Screen+Shot+2021-06-18+at+2.02.44+AM.png General Blog - Myocarditis and COVID-19 mRNA vaccines - Make it stand out Figure 3. Ammirati E, Veronese G, Bottiroli M, et al. Update on acute myocarditis. Trends Cardiovasc. Med. [electronic article]. 2020;(http://dx.doi.org/10.1016/j.tcm.2020.05.008) https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1624721384482-KFBXEJG0C3Z061GJOOPQ/Screen+Shot+2021-06-26+at+11.29.37+AM.png General Blog - Myocarditis and COVID-19 mRNA vaccines - Make it stand out Gourdie RG. The cardiac gap junction has discrete functions in electrotonic and ephaptic coupling: Gap junction function in cardiac conduction. Anat Rec (Hoboken) 2019;302(1):93–100. https://www.deplatformdisease.com/blog/covid-19-vaccines-probably-prevent-long-covid-pasc monthly 0.5 2021-06-16 https://www.deplatformdisease.com/blog/did-sars-cov-2-displace-influenza-through-viral-interference-it-seems-unlikely monthly 0.5 2021-06-07 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1623090323118-H7ORUZFDBSY530K9KO5K/Screen+Shot+2021-06-07+at+2.25.19+PM.png General Blog - Did SARS-CoV-2 cause the decline of influenza through viral interference? It seems unlikely. - Make it stand out You can see an inverse relationship between the incidence of rhinovirus infections and the incidence of influenza infections recorded from July 2016 to June 2019 at Yale New Haven Hospital. Influenza seems to peak around the time that rhinovirus declines; for rhinovirus a similar trend is noted but it seems less marked (seasonality seems to be weaker for rhinovirus than influenza). Note however that these data are retrospective and correlational so caution is needed in their interpretation. Wu, A., Mihaylova, V. T., Landry, M. L. & Foxman, E. F. Interference between rhinovirus and influenza A virus: a clinical data analysis and experimental infection study. Lancet Microbe 1, e254–e262 (2020). https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1623099675825-19NZ2MT5Y5NFEKY7ZMAQ/Screen+Shot+2021-06-07+at+5.01.12+PM.png General Blog - Did SARS-CoV-2 cause the decline of influenza through viral interference? It seems unlikely. - Make it stand out Petersen, E. et al. Comparing SARS-CoV-2 with SARS-CoV and influenza pandemics. Lancet Infect. Dis. 20, e238–e244 (2020) https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1623094459598-0KNHH948IN53M5LFX93A/Screen+Shot+2021-06-07+at+3.34.15+PM.png General Blog - Did SARS-CoV-2 cause the decline of influenza through viral interference? It seems unlikely. - Make it stand out Some examples of how viruses avoid host cell induction of interferon. García-Sastre, A. Ten strategies of interferon evasion by viruses. Cell Host Microbe 22, 176–184 (2017). https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1623093554139-MYPB6GZETU0GOLYWQZMK/Screen+Shot+2021-06-07+at+3.19.10+PM.png General Blog - Did SARS-CoV-2 cause the decline of influenza through viral interference? It seems unlikely. - Make it stand out Co-infection (where both pathogens are acquired at the same time) and superinfection (where hepatitis B is acquired first) have different trajectories in hepatitis D virus infection. This is considered the most severe form of viral hepatitis. Negro, F. Hepatitis D virus coinfection and superinfection. Cold Spring Harb. Perspect. Med. 4, a021550 (2014). https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1623098229771-5HA11NOJD4HMV4U3QG93/Screen+Shot+2021-06-07+at+4.37.05+PM.png General Blog - Did SARS-CoV-2 cause the decline of influenza through viral interference? It seems unlikely. - Make it stand out Preinfection with influenza results in worse outcomes in mice and enhanced SARS-CoV-2 replication in the respiratory tract. Bai, L. et al. Coinfection with influenza A virus enhances SARS-CoV-2 infectivity. Cell Res. 31, 395–403 (2021). https://www.deplatformdisease.com/blog/what-happens-when-the-pandemic-is-over monthly 0.5 2021-05-31 https://www.deplatformdisease.com/blog/spike-protein-circulating-in-the-vaccinated-what-does-it-mean monthly 0.5 2022-07-25 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1621616300166-88CLFXKEL7QOM8P3ZR10/Screen+Shot+2021-05-21+at+12.58.17+PM.png General Blog - Spike Protein Circulating in the Vaccinated: What does it mean? - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1621617359370-F9UJY1R3I6VQ5B3LJHHL/Screen+Shot+2021-05-21+at+1.15.52+PM.png General Blog - Spike Protein Circulating in the Vaccinated: What does it mean? - Make it stand out Plasma levels of vaccine antigens are shown on days after injection. Nucleocapsid is included as a negative control. The vaccines do not contain it, so if it is present, it may indicate that the spike antigens are from SARS-CoV-2 infection rather than from the vaccine. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1621628029564-AWDYUKBD5BQQWMED9ZUZ/Screen+Shot+2021-05-21+at+1.55.03+PM.png General Blog - Spike Protein Circulating in the Vaccinated: What does it mean? - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://www.deplatformdisease.com/blog/reverse-transcription-of-sars-cov-2-into-the-genome-a-brief-update monthly 0.5 2021-05-19 https://www.deplatformdisease.com/blog/vaccine-shedding-doesnt-work-like-that monthly 0.5 2021-05-17 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1621271114619-0BTGLCLKB68UYAVN658T/Screen+Shot+2021-05-17+at+1.05.05+PM.png General Blog - Vaccine Shedding Doesn’t Work Like That - Make it stand out Plotkin SA, Orenstein W, Offit PA, Edwards KM. Plotkin’s Vaccines. 7th ed. Philadelphia, PA: Elsevier - Health Sciences Division; 2017 Figure 37.4 showing the derivation of various lineages of the vaccine strain measles virus. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1621274388012-KRX7RP417ZBE8YIM2Y0E/Screen+Shot+2021-05-17+at+1.59.43+PM.png General Blog - Vaccine Shedding Doesn’t Work Like That - Make it stand out Nuismer SL, Bull JJ. Self-disseminating vaccines to suppress zoonoses. Nat Ecol Evol 2020;4(9):1168–73. https://www.deplatformdisease.com/blog/vaccine-nationalism-will-ensure-that-sars-cov-2-wins monthly 0.5 2021-04-30 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1619754929948-PCO4BJHWD89IORB5DEEL/Screen+Shot+2021-04-29+at+11.55.26+PM.png General Blog - Vaccine Nationalism Will Ensure That SARS-CoV-2 Wins Abdool Karim SS, de Oliveira T. New SARS-CoV-2 variants - clinical, public health, and vaccine implications. N Engl J Med [Internet]. 2021;(NEJMc2100362). Available from: http://dx.doi.org/10.1056/NEJMc2100362 https://www.deplatformdisease.com/blog/johnson-amp-johnsonjanssen-vaccine-pause monthly 0.5 2021-04-14 https://www.deplatformdisease.com/blog/q80hqi2mihc6k26mlde766tc9t0nnm monthly 0.5 2021-04-05 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1617558484257-142B6SCE4TE9MOTB06R9/Screen+Shot+2021-04-04+at+1.48.01+PM.png General Blog - MTHFR: Mostly Irrelevant Sbodio JI, Snyder SH, Paul BD. Regulators of the transsulfuration pathway: Modulating the transsulfuration pathway in disease. Br J Pharmacol. 2019;176(4):583–93. Figure 1 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1616883909135-8QERZ6VOE437UO2IX8D5/Screen+Shot+2021-03-27+at+6.25.06+PM.png General Blog - MTHFR: Mostly Irrelevant Zheng Y, Cantley LC. Toward a better understanding of folate metabolism in health and disease. J Exp Med. 2019;216(2):253–66. Figure 4 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1617577493790-N002XDD55CFIL50I800A/Screen+Shot+2021-04-04+at+7.04.46+PM.png General Blog - MTHFR: Mostly Irrelevant Ravanel S, Rébeillé F. Folate. In: Phytonutrients. Oxford, UK: Wiley-Blackwell; 2012. p. 173–202. Table 2 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1617255538650-HQV40AGKODKNQAHKV77C/Screen+Shot+2021-04-01+at+1.38.32+AM.png General Blog - MTHFR: Mostly Irrelevant Gerhard-Herman MD, Gornik HL, Barrett C, Barshes NR, Corriere MA, Drachman DE, et al. 2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease. J Am Coll Cardiol. 2017;69(11):e71–126. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1617255375378-X3XX88B3GAC89ZDN2IQS/Screen+Shot+2021-04-01+at+1.36.12+AM.png General Blog - MTHFR: Mostly Irrelevant Amsterdam EA, Wenger NK, Brindis RG, Casey DE Jr, Ganiats TG, Holmes DR Jr, et al. 2014 AHA/ACC guideline for the management of patients with non–ST-elevation acute coronary syndromes. J Am Coll Cardiol. 2014;64(24):e139–228. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1617125454803-7NYWVHDH96SM656UX1QU/Screen+Shot+2021-03-30+at+1.30.46+PM.png General Blog - MTHFR: Mostly Irrelevant Leung K-Y, Pai YJ, Chen Q, Santos C, Calvani E, Sudiwala S, et al. Partitioning of one-carbon units in folate and methionine metabolism is essential for neural tube closure. Cell Rep. 2017;21(7):1795–808. Figure 1 showing the partitioning of one-carbon metabolism between the mitochondria and cytosol, as well as the role of dietary folates and folic acid. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1616783524575-X1PDZ4O9M64GXUCECPZB/Screen+Shot+2021-03-26+at+2.32.01+PM.png General Blog - MTHFR: Mostly Irrelevant Berg JM, Tymoczko JL, Gatto GJ. Biochemistry. 8th ed. New York, NY: W.H. Freeman; 2015. Figure 24.9 The basic structure of tetrahydrofolate (this molecule may also be known as tetrahydropteroylglutamate); note the 3 major components of the molecule: the pteridine ring, the PABA linker, and a polyglutamate tail with variable length. Sources disagree on the number of glutamate linkers that may be present; dietary folates are said to commonly have 5 to 7, while some sources say no more than 5 linkers, and others say as many as 10. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1617578139324-0AHVI5VG8CD8CXF9Z2JY/Screen+Shot+2021-04-04+at+7.15.36+PM.png General Blog - MTHFR: Mostly Irrelevant Smith J, Gropper S, Carr T. Advanced nutrition and human metabolism. 8th ed. Belmont, CA: Wadsworth Publishing; 2021 Table 9.13 showing directly the different types of folate and their associated metabolic processes. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1616996410850-Z085VEJ8LWWMBOCYND5G/Screen+Shot+2021-03-29+at+1.40.06+AM.png General Blog - MTHFR: Mostly Irrelevant Ducker GS, Rabinowitz JD. One-carbon metabolism in health and disease. Cell Metab. 2017;25(1):27–42. Figure 1 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1616889260808-AU5Q0HTG0EF27VH10ZDD/Screen+Shot+2021-03-27+at+7.54.17+PM.png General Blog - MTHFR: Mostly Irrelevant RCSB Protein Data Bank. 6FCX [Internet]. Rcsb.org. [cited 2021 Mar 27]. Available from: https://www.rcsb.org/structure/6FCX The x-ray crystal structure of the MTHFR homodimer. A tetrameric form is known to occur in bacteria but the homodimer is thought to be the principal form in humans. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1616904907813-AKQQ2GSNNWCIZATVYXFS/Screen+Shot+2021-03-28+at+12.15.03+AM.png General Blog - MTHFR: Mostly Irrelevant Molloy AM, Pangilinan F, Brody LC. Genetic risk factors for folate-responsive neural tube defects. Annu Rev Nutr. 2017;37:269–91. Some purists argue that encephalocele and meningocele are not true neural tube defects because they involve the cranial mesoderm, rather than the neuroectoderm as true neural tube defects do. However, folic acid supplementation has been shown to prevent these as well. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1617255137767-PC95H5WPAE716W911E4E/Screen+Shot+2021-04-01+at+1.32.15+AM.png General Blog - MTHFR: Mostly Irrelevant Fihn SD, Gardin JM, Abrams J, Berra K, Blankenship JC, Dallas AP, et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease. J Am Coll Cardiol. 2012;60(24):e44–164. https://www.deplatformdisease.com/blog/azclots monthly 0.5 2021-03-25 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1616534274544-ITD31UI7OO903CYJJN9G/Screen+Shot+2021-03-23+at+5.17.24+PM.png General Blog - Is the Oxford/AZ COVID-19 Vaccine causing blood clots? Hoffman, R. et al. Hematology: Basic principles and practice. (Elsevier - Health Sciences Division, 2017) Box 139.1 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1616534717523-DNL28362U856IM1XTOVI/Screen+Shot+2021-03-23+at+5.24.35+PM.png General Blog - Is the Oxford/AZ COVID-19 Vaccine causing blood clots? Greinacher, A. Heparin-induced thrombocytopenia. N. Engl. J. Med. 373, 252–261 (2015). Figure 1 summarizing the pathomechanism for HIT. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1616372369043-6OHOS9HJKHZ8Z6EI6KL3/Screen+Shot+2021-03-21+at+8.19.21+PM.png General Blog - Is the Oxford/AZ COVID-19 Vaccine causing blood clots? Risk of venous thromboembolism among users of drospirenone-containing oral contraceptive pills. Acog.org https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2012/11/risk-of-venous-thromboembolism-among-users-of-drospirenone-containing-oral-contraceptive-pills. Note that though this is a real and recognized risk for the use of OCPs, they are taken frequently anyway because (1) the risk of the event is greater in pregnancy and the postpartum period and (2) the benefits of the OCPs are thought to outweigh the risks. This is the exact situation we find ourselves in with COVID-19 and the Oxford/AZ vaccine. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1616372843891-H7YRD0UUTGT7G5YW0IDL/Screen+Shot+2021-03-21+at+8.27.20+PM.png General Blog - Is the Oxford/AZ COVID-19 Vaccine causing blood clots? COVID-19 Vaccine AstraZeneca: benefits still outweigh the risks despite possible link to rare blood clots with low blood platelets. Europa.eu https://www.ema.europa.eu/en/news/covid-19-vaccine-astrazeneca-benefits-still-outweigh-risks-despite-possible-link-rare-blood-clots. Summary of patient information from the EMA https://www.deplatformdisease.com/blog/covid-19-vaccine-animal-studies monthly 0.5 2021-03-17 https://www.deplatformdisease.com/blog/addressing-geert-vanden-bossches-claims monthly 0.5 2021-03-19 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1615837248597-U9V49A9RGHWH6NY13PGI/Screen+Shot+2021-03-15+at+3.40.23+PM.png General Blog - Addressing Geert Vanden Bossche’s Claims An extremely incorrect depiction of dendritic cell-NK cell interactions made by Geert Vanden Bossche. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1615833794736-19L4U6ESVGGE6K2R0E74/Screen+Shot+2021-03-15+at+2.42.47+PM.png General Blog - Addressing Geert Vanden Bossche’s Claims Wang Z, Schmidt F, Weisblum Y, et al. mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. Nature [Internet] 2021;Available from: https://www.nature.com/articles/s41586-021-03324-6.pdf Figure 1i; note that in some individuals there is preserved antibody neutralization with the constellation of problematic mutations in the spike protein that are noted to reduce binding affinity. Red circles indicate that the patient received Pfizer’s vaccine while white circles indicate Moderna’s vaccine. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1615835454511-5O62L1ZFEYN7V9E1Y2LC/Screen+Shot+2021-03-15+at+3.10.51+PM.png General Blog - Addressing Geert Vanden Bossche’s Claims Murphy K, Weaver C. Janeway’s Immunobiology. 9th ed. Boca Raton, FL: CRC Press; 2016. Table 10.27 https://www.deplatformdisease.com/blog/fetal-cell-use-in-vaccines monthly 0.5 2021-03-09 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1615176745285-TNACMHT0DDAG8OWJHKC7/Screen+Shot+2021-03-07+at+11.12.22+PM.png General Blog - Fetal tissue use in vaccines Lodish H, Berk A, Kaiser CA, et al. Molecular Cell Biology. 8th ed. W.H. Freeman; 2016. Figure 4.1 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1615312858542-S43VERYIP464VT9X8378/Screen+Shot+2021-03-09+at+1.00.38+PM.png General Blog - Fetal tissue use in vaccines Moremen KW, Tiemeyer M, Nairn AV. Vertebrate protein glycosylation: diversity, synthesis and function. Nat Rev Mol Cell Biol. 2012;13(7):448-462 Box 1 demonstrating the major types of glycosylation patterns observed from vertebrates. https://www.deplatformdisease.com/blog/hpv-vaccine-truth-and-fiction monthly 0.5 2023-01-21 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1614472899004-8Q6MCGFB31SUGC8KCA9F/Screen+Shot+2021-02-27+at+7.41.37+PM.png General Blog - HPV Vaccines: Separating Truth from Fiction Adverse Effects of Vaccines: Evidence and Causality (2012) Chapter: 9 Human Papillomavirus Vaccine. Nap.edu. [accessed 2021a Feb 28]. https://www.nap.edu/read/13164/chapter/11#520. Causality judgments from the IOM https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1614389909805-A92XSHZ9BV4XWMP555QB/Screen+Shot+2021-02-26+at+8.38.26+PM.png General Blog - HPV Vaccines: Separating Truth from Fiction Guo F, Cofie LE, Berenson AB. 2018. Cervical cancer incidence in young U.s. females after human Papillomavirus vaccine introduction. Am J Prev Med. 55(2):197–204. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1614321994001-QQWYOA9265YSD18PEPA6/Screen+Shot+2021-02-26+at+1.46.30+AM.png General Blog - HPV Vaccines: Separating Truth from Fiction Plotkin SA, Orenstein W, Offit DPA, Edwards KM. 2017. Plotkin’s Vaccines. 7th ed. Elsevier. Table 30.3 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1614278547544-B7SCOW45ZY55GEPTMDKC/Screen+Shot+2021-02-25+at+1.42.23+PM.png General Blog - HPV Vaccines: Separating Truth from Fiction An HPV virus-like particle as visualized by cryoelectron microscopy. The outer structures are the L1 protein of HPV. This is made from 360 copies of the protein. The inside of the particle is empty. Smith DM, Simon JK, Baker JR Jr. 2013. Applications of nanotechnology for immunology. Nat Rev Immunol. 13(8):592–605. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1614281503888-ND1FFPO7ITO6COV8OQMC/Screen+Shot+2021-02-25+at+2.31.41+PM.png General Blog - HPV Vaccines: Separating Truth from Fiction A BPV (bovine papillomavirus- a relative of human papillomaviruses) visualized by cryoelectron microscopy, with DNA underneath reconstructed in (B). Note the similarity to the virus-like particle. From Buck CB, Cheng N, Thompson CD, et al. Arrangement of L2 within the papillomavirus capsid. J Virol 2008;82:5190–5197 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1614307223705-TDCBUUQ2MG9M748RDPFU/Screen+Shot+2021-02-25+at+9.40.03+PM.png General Blog - HPV Vaccines: Separating Truth from Fiction Celentano DD, Szklo M, Gordis L. 2018. Gordis Epidemiology. 6th ed. Elsevier. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1614385327118-C28DX2G4WT6MWB1VPIS2/Screen+Shot+2021-02-26+at+7.22.04+PM.png General Blog - HPV Vaccines: Separating Truth from Fiction Plotkin SA, Orenstein W, Offit DPA, Edwards KM. 2017. Plotkin’s Vaccines. 7th ed. Elsevier. Figure 30.7 https://www.deplatformdisease.com/blog/vitamin-d-is-not-a-substitute-for-any-vaccine monthly 0.5 2021-04-24 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1612501572404-8ZO3WDBEDV1J1ENQN2SJ/Screen+Shot+2021-02-05+at+12.05.27+AM.png General Blog - Vitamin D is not a substitute for any vaccine Pike JW, Christakos S. 2017. Biology and mechanisms of action of the vitamin D hormone. Endocrinol Metab Clin North Am. 46(4):815–843. Figure 3 demonstrating the cell biology of vitamin D’s genomic actions. Calcitriol is able to bind the vitamin D receptor (VDR) which forms a heterodimer complex with the retinoid X receptor (RXR) and recognizes sequences in the DNA known as vitamin D response elements (VDREs). Co-repressor proteins associated with the VDR/RXR heterodimer dissociate and allow for the mediator complex to be recruited to the site, where it can modify histones with readers, writers, and erasers. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1611100258879-LVOF2DB78K9WPLC88DH4/image-asset.png General Blog - Vitamin D is not a substitute for any vaccine Bouillon, R. (2017). Comparative analysis of nutritional guidelines for vitamin D. Nature Reviews Endocrinology, 13(8), 466–479. Figure 3 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1611123387139-6KZGBPMWD6PBG9WY8SCX/Screen+Shot+2021-01-20+at+1.16.23+AM.png General Blog - Vitamin D is not a substitute for any vaccine Christakos, S., Dhawan, P., Verstuyf, A., Verlinden, L., & Carmeliet, G. (2016). Vitamin D: Metabolism, molecular mechanism of action, and pleiotropic effects. Physiological Reviews, 96(1), 365–408 Figure 9 demonstrated 1,25(OH)2D3, the highly active form of vitamin D. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1611098254080-BTNYPS82S44K7CGKJHRQ/image-asset.png General Blog - Vitamin D is not a substitute for any vaccine Jameson, J. L., & De Groot, L. J. (2015). Endocrinology: Adult and pediatric, 2-volume set (7th ed.). Philadelphia, PA: Saunders Figure 59-2 summarizing the pathways for making and breaking down vitamin D and its precursors. The sequence of reactions up to the production of 7-dehydrocholesterol is known as the Kandutsch-Russell pathway, and is found to occur primarily in skin, muscle, and brain tissue, though of these only skin can significantly contribute to vitamin D production due to the need for UV exposure. In other tissues, the Bloch pathway produces zymosterol instead of 7-dehydrocholesterol, and thus these cannot serve as a site for vitamin D production. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1612501967323-PLLNOBNA38OI3I761AUZ/Screen+Shot+2021-02-05+at+12.12.44+AM.png General Blog - Vitamin D is not a substitute for any vaccine Boron WF, Boulpaep EL. 2016. Medical Physiology. 3rd ed. Philadelphia, PA: Elsevier - Health Sciences Division. Figure 52-1 on calcium balance in the body. See text for details https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1612136359134-CKDPIGI746WLAL89UD5J/Screen+Shot+2021-01-31+at+6.39.02+PM.png General Blog - Vitamin D is not a substitute for any vaccine Mason RS, Rybchyn MS, Abboud M, Brennan-Speranza TC, Fraser DR. 2019. The role of skeletal muscle in maintaining vitamin D status in winter. Curr Dev Nutr. 3(10):nzz087 Figure 1 demonstrating storage of vitamin D within the liver. There is an active exchange of 25-OH-D with the circulation and skeletal muscle cells. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1612136899393-5L2P22T5T2PSCIH8U96C/Screen+Shot+2021-01-31+at+6.47.54+PM.png General Blog - Vitamin D is not a substitute for any vaccine Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G. 2016. Vitamin D: Metabolism, molecular mechanism of action, and pleiotropic effects. Physiol Rev. 96(1):365–408. Figure 6 demonstrating the context dependent effects of vitamin D. In the state of negative calcium balance, bone, the calcium reservoir, releases calcium into the blood with the aid of osteoclasts, whose production is promoted by vitamin D by enhancing expression of RANKL. On the other hand, if there is excess serum calcium, vitamin D appears to promote bone mineralization, but the mechanisms by which this occurs are not well characterized other than a reduction in the expression of RANKL by osteoblasts. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1613369430505-X0QZUC5PFIKX1HFUX392/Screen+Shot+2021-02-15+at+1.10.26+AM.png General Blog - Vitamin D is not a substitute for any vaccine Rosen CJ, Taylor CL. 2013. Common misconceptions about vitamin D—implications for clinicians. Nat Rev Endocrinol. 9(7):434–438. Figure 2 showing average vitamin D levels by age group with 50 nmol/L representing the level of 25-OH-D at which additional health benefits stop being observed. The implication is that claims about the pervasiveness of deficiency across the US are likely unfounded, and indeed the IOM has found 97.5% of the US population to be vitamin D replete. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1612136669089-7K5GND73MVPBSBY0VA8F/Screen+Shot+2021-01-31+at+6.44.21+PM.png General Blog - Vitamin D is not a substitute for any vaccine Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G. 2016. Vitamin D: Metabolism, molecular mechanism of action, and pleiotropic effects. Physiol Rev. 96(1):365–408. Figure 4 demonstrating vitamin D effects on the kidneys. Principally, vitamin D functions to prevent excretion of calcium into the urine. The mechanisms by which this is accomplished are similar to those in IECs, though the VDR complex with calcitriol is thought to play a more important role. TRPV5 and TRPV6 are the major calcium transporters which facilitate diffusion of the ion into the cell, wherein it is picked up by calbindin-D9k or calbindin-D28k and transported to the basolateral surface of the cell. Therein, PMCA1b or the sodium-calcium exchanger 1(NCX1) extrude the calcium back into the blood. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1612136554117-4VSS5I1SS7NK21B2K30L/Screen+Shot+2021-01-31+at+6.42.30+PM.png General Blog - Vitamin D is not a substitute for any vaccine Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G. 2016. Vitamin D: Metabolism, molecular mechanism of action, and pleiotropic effects. Physiol Rev. 96(1):365–408. Figure 3 demonstrating the effects of vitamin D on intestinal epithelial cells (IECs). One of the most critical roles of vitamin D is to ensure the uptake of calcium enterically from IECs. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1613434526599-DRGSVESVU1JG8FA96O92/Screen+Shot+2021-02-15+at+7.14.47+PM.png General Blog - Vitamin D is not a substitute for any vaccine Li YC. 2011. Vitamin D and the Renin-Angiotensin System. In: Vitamin D. Elsevier. p. 707–723. Figure 40.1 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1613279162771-6CI08BZYT6FLIYXTOGPF/Screen+Shot+2021-02-14+at+12.05.44+AM.png General Blog - Vitamin D is not a substitute for any vaccine Patchen BK, Clark AG, Hancock DB, Gaddis N, Cassano PA. 2021. Genetically predicted serum vitamin D and COVID-19: a Mendelian randomization study. bioRxiv. doi:10.1101/2021.01.29.21250759. https://www.medrxiv.org/content/10.1101/2021.01.29.21250759v1.full.pdf. Figure 3 summarizing the results of the MR estimates. There is no significant association for instrument A (the genes relating to vitamin D function) show no effect for any of the parameters. This is also the case for instrument C, which includes expanded loci for genes associated with vitamin D function. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1613520479073-4US90KETP497LLRKINYY/Screen+Shot+2021-02-16+at+7.07.55+PM.png General Blog - Vitamin D is not a substitute for any vaccine Jameson, J. L., & De Groot, L. J. (2015). Endocrinology: Adult and pediatric, 2-volume set (7th ed.). Philadelphia, PA: Saunders Figure 59-6 summarizing the immunological effects of vitamin D on the endocrine system. Broadly, vitamin D seems to promote tolerance and suppress responses by the induction of anti-inflammatory cytokines and suppression of pro-inflammatory cytokines. Note that it also suppresses antibody production and plasma cell differentiation, which are critical in the establishment of humoral immune memory. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1611519593019-QWXGFZH64CAJRYBBI038/image-asset.png General Blog - Vitamin D is not a substitute for any vaccine Brunton L, Knollman B, Hilal-Dandan R. 2017. Goodman and Gilman’s the pharmacological basis of therapeutics, 13th edition. McGraw-Hill Education/Medical Table 48.1 The recommended daily allowance of vitamin D per the IOM standards established in 2011 (sufficient for 97.5% of the population). https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1611525671748-IY0IP2Y0EP16NJH7PDG5/Screen+Shot+2021-01-24+at+4.57.55+PM.png General Blog - Vitamin D is not a substitute for any vaccine Jameson JL, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J. 2018. Harrison’s Principles of Internal Medicine 20th Edition. 20th ed. Columbus, OH: McGraw-Hill Education. Figure 400-2 demonstrating the manner in which fats circulate throughout the body. This is divided into an exogenous pathway wherein dietary fats are transported to the periphery and then the liver and an endogenous pathway wherein fats are transported from the liver to the periphery. Fats can be absorbed from the diet wherein they are packaged into chylomicrons and get distributed to other tissues. Chylomicrons have apolipoproteins associated with their surfaces that assist with uptake into target tissues, which express lipoprotein lipase. This liberates fats, in particular cholesterol, and then the chylomicron remnants circulate back to the liver, which recognizes the remnants via the LDL receptor (which recognizes ApoB). The liver in turn produces bile acids and cholesterol that esterify dietary fats, and releases VLDL back to the circulation, which tissues take up and then produce IDL. IDL returns to the liver via the circulation and the LDL receptor and is converted to LDL, which returns to peripheral tissues. Peripheral tissues can initiate reverse cholesterol transport wherein they supply cholesterol to HDL to return it back to the liver. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1611525198889-I7EH8NSPSTSY7ZSK6ISE/Screen+Shot+2021-01-24+at+4.52.58+PM.png General Blog - Vitamin D is not a substitute for any vaccine Jameson, J. L., & De Groot, L. J. (2015). Endocrinology: Adult and pediatric, 2-volume set (7th ed.). Philadelphia, PA: Saunders Figure 59-1 demonstrating the distribution of vitamin D. Vitamin D is initially found as part of chylomicrons when produced enterically, but most vitamin D is associated with vitamin D binding protein (DBP), a smaller proportion is associated with albumin, and a very small fraction exists as free vitamin D. Metabolism of the vitamin D is performed as above, wherein it can act on target cells expressing the vitamin D receptor. Vitamin D can be taken up associated with DBP via a process assisted by megalin and cubulin or in its free form. In general, the free hormone is considered to be the major biologically active form of vitamin D. Vitamin D receptors express the RXR motif and recognize vitamin D response elements (VDRE) in the DNA to alter gene transcription in the same manner as other steroids (see “Cell biology and Mechanism of Action” section for details). https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1612036726607-VJ0XPDZCXNUIFZKYS1ER/Screen+Shot+2021-01-30+at+2.58.43+PM.png General Blog - Vitamin D is not a substitute for any vaccine Mark A. Sperling, MD, Joseph A. Majzoub, MD Ram K. Menon, MD, FRCP Constantine A. Stratakis, MD, D(MED)Sc, PhD(hc). 2021. Sperling Pediatric Endocrinology 5th Edition. Philadelphia: Elsevier. Figure 9.5 demonstrating the regulation of vitamin D at the cellular level. Under basal conditions, the complex of VDR (vitamin D receptor) /RXR (retinoid-X receptor) with VDIR (Vitamin D-interacting repressor) and WINAC (WSTF (Williams Syndrome Transcription Factor) including nucleosome assembly complex) are associated with vitamin D response elements and a histone deacetylase (HDAC). These suppress transcription of 24-hydroxylase which initiates the breakdown of calcitriol (active vitamin D). However, upon binding of calcitriol, the HDAC is replaced and instead a histone acetyltransferase activation complex (p300/CBP), acetylates the lysines of the histone to recruit transcription machinery and trigger production of 24-hydroxylase that will induce vitamin D breakdown. Alternatively, vitamin D can suppress production of 1α-hydroxylase, which generates calcitriol, by recruiting HDACs on binding that silence transcription. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1612986771739-1IL00M9LUY8OA9G0L1NK/Screen+Shot+2021-02-10+at+2.52.26+PM.png General Blog - Vitamin D is not a substitute for any vaccine Martineau AR, Jolliffe DA, Hooper RL, Greenberg L, Aloia JF, Bergman P, Dubnov-Raz G, Esposito S, Ganmaa D, Ginde AA, et al. 2017. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ.:i6583. Figure 2 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1613517698831-G1H5KTLTULWODRCXLPB5/Screen+Shot+2021-02-16+at+6.21.19+PM.png General Blog - Vitamin D is not a substitute for any vaccine Pilz S, Verheyen N, Grübler MR, Tomaschitz A, März W. 2016. Vitamin D and cardiovascular disease prevention. Nat Rev Cardiol. 13(7):404–417 Figure 2 summarizing some of the known extraskeletal effects of vitamin D. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1613518261291-N41GTAXR4D41EYGBM89L/Screen+Shot+2021-02-16+at+6.30.58+PM.png General Blog - Vitamin D is not a substitute for any vaccine Pilz S, Verheyen N, Grübler MR, Tomaschitz A, März W. 2016. Vitamin D and cardiovascular disease prevention. Nat Rev Cardiol. 13(7):404–417 Table 2 summarizing the results of meta-analyses of RCTs examining vitamin D supplementation on cardiovascular risk. None of the results are statistically significant and the actual point estimates are variable regarding a benefit or a detriment, suggesting that there is likely no clinically important effect. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1613538780124-XMUM7H012G1JJUM3DHGM/Screen+Shot+2021-02-17+at+12.12.56+AM.png General Blog - Vitamin D is not a substitute for any vaccine Stipanuk MH, Caudill MA. 2012. Biochemical, physiological, and molecular aspects of human nutrition. 3rd ed. London, England: W B Saunders. Figure 31-5. https://www.deplatformdisease.com/blog/an-overview-of-us-vaccine-pharmacovigilance monthly 0.5 2021-04-22 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1612389740324-ZKKNSY1J4CQIONURE3V6/Screen+Shot+2021-02-03+at+5.02.14+PM.png General Blog - US Vaccine Pharmacovigilance: Your Friend is Probably Using VAERS Incorrectly Strom, B. L., Kimmel, S. E., & Hennessy, S. (Eds.). (2019). Pharmacoepidemiology. Wiley. Table 20.2 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1612238760433-FM6WSK2H6GLYJFOTDY8E/image-asset.png General Blog - US Vaccine Pharmacovigilance: Your Friend is Probably Using VAERS Incorrectly A sampling of some things reported to VAERS. ID numbers are included so that the events can be verified. Note however that VAERS recently switched to a 7-digit ID system so you need to write a “0” before the stated IDs to find the report. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1612319252427-IZZNE61ZKTLGGY1WOB9O/image-asset.png General Blog - US Vaccine Pharmacovigilance: Your Friend is Probably Using VAERS Incorrectly Plotkin, S. A., Orenstein, W., Offit, D. P. A., & Edwards, K. M. (2017). Plotkin’s Vaccines (7th ed.). Elsevier. Table 82.2. demonstrating an example of how one might go about determining whether or not a causal relationship exists between a vaccine and an associated adverse event. As you might guess, it requires quite a bit of expertise. Firstly one has to have an intimate understanding of the biology of the adverse event and vaccine in question so that they can define an appropriate risk interval. From there, it’s a bunch of hard-core, good old-fashioned epidemiology: you compare the rate in the vaccinated cohort to the background rate to see whether or not there is a true increase in the incidence. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1612413332069-L3EZYIWWM809QCEY2JN3/Screen+Shot+2021-02-03+at+11.35.13+PM.png General Blog - US Vaccine Pharmacovigilance: Your Friend is Probably Using VAERS Incorrectly Strom, B. L., Kimmel, S. E., & Hennessy, S. (Eds.). (2019). Pharmacoepidemiology. Wiley. Figure 20.1 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1612382755507-WZAN33CGW3J2MG56CCRC/image-asset.jpeg General Blog - US Vaccine Pharmacovigilance: Your Friend is Probably Using VAERS Incorrectly Shimabukuro, T. (n.d.). COVID-19 vaccine post-authorization safety monitoring update. Retrieved February 3, 2021, from Cdc.gov website: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2020-12/COVID-04-Shimabukuro.pdf A summary of the monitoring systems put in place for vaccine pharmacovigilance focusing on the COVID-19 vaccines. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1612415196246-CJS04JAHEXZV8TGRNB6N/Screen+Shot+2021-02-04+at+12.05.47+AM.png General Blog - US Vaccine Pharmacovigilance: Your Friend is Probably Using VAERS Incorrectly Slide courtesy of Dr. Bob Wachter: https://twitter.com/Bob_Wachter/status/1333966348972539904?s=20 IMPORTANT CLARIFICATION PLEASE READ: These values reflect the background rate of these conditions. For any given random sample of 10 million people over a period of 2 months we can expect these quantities of these health outcomes. If they happen to get a vaccine 2 months beforehand, the events will be associated with the vaccination even though they have no relationship. This is why caution is needed in assessing individual events- they may reflect background incidence. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1612380140997-P4W6X40N81B4N56B573I/Screen+Shot+2021-02-03+at+2.22.00+PM.png General Blog - US Vaccine Pharmacovigilance: Your Friend is Probably Using VAERS Incorrectly Strom, B. L., Kimmel, S. E., & Hennessy, S. (Eds.). (2019). Pharmacoepidemiology. Wiley. Table 20.2 https://www.deplatformdisease.com/blog/being-a-vaccine-advocate-on-social-media monthly 0.5 2021-01-06 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1609884668387-8ERU143VIXQ1ERX67EKN/Screen+Shot+2021-01-05+at+5.11.01+PM.png General Blog - Being a Vaccine Advocate on Social Media Here are some resources to help you: https://vaxopedia.org/2019/01/05/how-to-become-a-vaccine-advocate/?fbclid=IwAR2cv29C5x-NzHZCbcGD6Y7LIzQqqjWN1eX3NbLNizAYuU2ydoWTdFQ4h4s https://www.immunizeca.org/education-hour/?fbclid=IwAR0MsA1SZZOrI-UG7O1Y03HRQyLSmqTYin2CXT35YxKwtsYPkU_QhRnUuHs https://www.deplatformdisease.com/blog/how-many-doses-of-the-covid-19-vaccine-are-needed monthly 0.5 2021-01-02 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1609545543481-EX2KWSPR5FGXSKL1KIFZ/image-asset.png General Blog - B.1.1.7: How many doses of the COVID-19 vaccine are needed? Rich. 2018. Clinical immunology: Principles and practice. 5th ed. London, England: Elsevier Health Sciences. Figure 15.3 Antibodies in general recognize conformational epitopes because they see proteins in 3 dimensional space. Sometimes, the conformational epitope is the same as the linear epitope. Because T cells recognize processed antigens, they recognize linear epitopes only. Thus modeling that examines only linear epitopes without considering how proteins folds does not fully account for the immune response https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1609544181779-SWCHDTM66G4JYO1RSGRR/image-asset.jpeg General Blog - B.1.1.7: How many doses of the COVID-19 vaccine are needed? Professor Vineet Menachery reported this PRNT comparing neutralization of wild type SARS-CoV-2 and N501Y variants. There isn’t any significant difference. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1609542744408-FD19C3RC701Z17R76PZA/Screen+Shot+2021-01-01+at+6.12.21+PM.png General Blog - B.1.1.7: How many doses of the COVID-19 vaccine are needed? https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1609547351300-FIDEA8O9Y7S3T947LJOF/image-asset.png General Blog - B.1.1.7: How many doses of the COVID-19 vaccine are needed? Walsh EE, Frenck RW Jr, Falsey AR, Kitchin N, Absalon J, Gurtman A, Lockhart S, Neuzil K, Mulligan MJ, Bailey R, et al. 2020. Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates. N Engl J Med. 383(25):2439–2450. Figure 4 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1609548363616-46WMS5T0UZW98X6LOHYH/modernafigure.png General Blog - B.1.1.7: How many doses of the COVID-19 vaccine are needed? Anderson EJ, Rouphael NG, Widge AT, Jackson LA, Roberts PC, Makhene M, Chappell JD, Denison MR, Stevens LJ, Pruijssers AJ, et al. 2020. Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults. N Engl J Med. 383(25):2427–2438. Figure 2 https://www.deplatformdisease.com/blog/vaccines-and-anaphylaxis-a-primer monthly 0.5 2021-03-18 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1608944295120-Y14P68O1PCHFGQSLL4G6/Screen+Shot+2020-12-25+at+7.58.09+PM.png General Blog - Vaccines and Anaphylaxis: Everything You Ever Wanted To Know McNeil MM, DeStefano F. 2018. Vaccine-associated hypersensitivity. J Allergy Clin Immunol. 141(2):463–472. Table II https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1608836110033-8ZUN2GJQHZKD96KIUJP1/F1.large.jpg General Blog - Vaccines and Anaphylaxis: Everything You Ever Wanted To Know Gowthaman U, Chen JS, Zhang B, Flynn WF, Lu Y, Song W, Joseph J, Gertie JA, Xu L, Collet MA, et al. 2019. Identification of a T follicular helper cell subset that drives anaphylactic IgE. Science. 365(6456):eaaw6433 summary figure. T follicular helper cells (Tfhs) are important partner cells in the production of antibodies and guide B cells in terms of the type of antibodies they make. Tfh cells can induce different types of antibodies depending on the type of antigen they encounter. A population of Tfh cells called Tfh13 cells produces high levels of IL-4, IL-5, and IL-13, and low levels of IL-21, which seem to induce B cells to generate high-affinity IgE that drives anaphylaxis. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1608857603282-XNEHVMQM24KATB800P6H/Screen+Shot+2020-12-24+at+7.53.17+PM.png General Blog - Vaccines and Anaphylaxis: Everything You Ever Wanted To Know Gao Y, Han Y, Zhang X, Fei Q, Qi R, Hou R, Cai R, Peng C, Qi Y. 2020. Penicillin causes non-allergic anaphylaxis by activating the contact system. Sci Rep. 10(1):14160. Figure 7 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1608867030778-F2WWRPU3GSTANUD3K2KA/Screen+Shot+2020-12-24+at+10.30.09+PM.png General Blog - Vaccines and Anaphylaxis: Everything You Ever Wanted To Know Adkinson NF Jr, Bochner BS, Burks DAW, Busse PWW, Holgate PST, Lemanske DRF Jr, O’Hehir PRE. 2013. Middleton’s allergy 2-volume set: Principles and practice (expert consult premium edition - enhanced online features and print). 8th ed. Philadelphia, PA: Saunders Table 77-6 summarizing the typical symptoms and signs that occur in anaphylaxis and their frequency. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1607657501153-C3059EITH7S6YT4T8GU2/image-asset.png General Blog - Vaccines and Anaphylaxis: Everything You Ever Wanted To Know Simons FER, Ardusso LR, Bilò MB, Cardona V, Ebisawa M, El-Gamal YM, Lieberman P, Lockey RF, Muraro A, Roberts G, et al. 2014. International consensus on (ICON) anaphylaxis. World Allergy Organ J. 7(1):9. Table 2 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1608859620868-SPQ3G25H12AFLNIZTUR3/Screen+Shot+2020-12-24+at+8.26.54+PM.png General Blog - Vaccines and Anaphylaxis: Everything You Ever Wanted To Know Busse PJ, Christiansen SC. 2020. Hereditary angioedema. N Engl J Med. 382(12):1136–1148.The mechanism by which bradykinin causes angioedema. Mannose-binding lectin associated serine protease 1 (MASP1) is able to cleave the complex of high molecular weight kininogen and kallikrein (formed from prekallikrein that is cleaved by activated factor XII) to release bradykinin. Bradykinin, then, via the bradykinin B2 receptor can go on to induce vasodilation that promotes vascular leakage; the role of the B1 receptor in this process is not as well understood. Bradykinin can be inhibited with the drug icatibant, which binds B2 receptors to block bradykinin signaling. Additionally, bradykinin is broken down by ACE into des-Arg-bradykinin which is a generally inactive product but can weakly bind the B1 receptor. Bradykinin is also broken down by carboxypeptidase N and M. C1 inhibitor blocks the synthesis of bradykinin at multiple points in the synthetic pathway. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1608962782675-8LATYX4Z2R378ZXM13J8/image-asset.png General Blog - Vaccines and Anaphylaxis: Everything You Ever Wanted To Know Castells M. 2017. Diagnosis and management of anaphylaxis in precision medicine. J Allergy Clin Immunol. 140(2):321–333. Figure 1A; Anaphylaxis can be grouped into 4 categories (endotypes). The first involves massive activation of mast cells or basophils by IgE or an IgE-independent mechanism (type 1 anaphylaxis). Sometimes certain chemotherapies and monoclonal antibodies can produce anaphylaxis reactions wherein there is massive cytokine release, and these may also present in a mixed form which resembles type 1 anaphylaxis. Complement has also been proposed as being capable of inducing anaphylaxis in response to contrast dyes, dialysis membranes, and glycosaminoglycans. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1608842245236-65Q5GVJSTPKK5CJDID58/image-asset.png General Blog - Vaccines and Anaphylaxis: Everything You Ever Wanted To Know Subramanian H, Gupta K, Ali H. 2016. Roles of Mas-related G protein–coupled receptor X2 on mast cell–mediated host defense, pseudoallergic drug reactions, and chronic inflammatory diseases. J Allergy Clin Immunol. 138(3):700–710 Figure 3 demonstrating the putative mechanism by which MRGPRX2 signaling occurs and can mediate pseudo-allergic reactions including non-allergic anaphylaxis. In general, binding of various substrates seems to induce import of calcium through calcium release–activated calcium channel (ORAI) which then triggers multiple downstream signaling pathways that result in mast cell degranulation. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1608866865941-CCWS1D9T3O5WMJYAR6MH/Screen+Shot+2020-12-24+at+10.27.39+PM.png General Blog - Vaccines and Anaphylaxis: Everything You Ever Wanted To Know Lee S, Bellolio MF, Hess EP, Campbell RL. 2014. Predictors of biphasic reactions in the emergency department for patients with anaphylaxis. J Allergy Clin Immunol Pract. 2(3):281–287. Table 2, predictors of biphasic anaphylaxis (indicators found to be predictive are denoted with asterisks in the rightmost column). https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1607658504182-1PNZX81FKB8XQVOQ8XFL/Screen+Shot+2020-12-10+at+10.48.18+PM.png General Blog - Vaccines and Anaphylaxis: Everything You Ever Wanted To Know Adkinson NF Jr, Bochner BS, Burks DAW, Busse PWW, Holgate PST, Lemanske DRF Jr, O’Hehir PRE. 2013. Middleton’s allergy 2-volume set: Principles and practice (expert consult premium edition - enhanced online features and print). 8th ed. Philadelphia, PA: Saunders Table 77-4 describing the different mast cell and basophil mediators and their role in anaphylaxis. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1608841766222-VYX9V2NQO23TJ1XW8PEW/image-asset.png General Blog - Vaccines and Anaphylaxis: Everything You Ever Wanted To Know Owen J, Punt J, Stranford S. 2013. Kuby Immunology: International Edition. 7th ed. New York, NY: W.H. Freeman. Summarizing the basic mechanisms of different allergies; most allergies are due to type 1 (immediate) hypersensitivity reactions, and allergic anaphylaxis is an example. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1608944642886-J9LNL8LUOLFN8U6WKD3R/image-asset.png General Blog - Vaccines and Anaphylaxis: Everything You Ever Wanted To Know Interim clinical considerations for use of Pfizer-BioNTech COVID-19 Vaccine. 2020 Dec 21. Cdc.gov. [accessed 2020 Dec 26]. https://www.cdc.gov/vaccines/covid-19/info-by-product/clinical-considerations.html?fbclid=IwAR3NqhqiqaQVbeuCQiTXFwK0gydabblnvEAxmiKNW8lYFMdbwc0QhlTI9Gk. https://www.deplatformdisease.com/blog/does-sars-cov-2-have-a-reverse-transcriptase monthly 0.5 2020-12-17 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1608157605364-UQXC3H0WB2SA4KDMHF3C/image-asset.png General Blog - Does SARS-CoV-2 reverse transcribe and integrate into our genome? https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1608157768746-ZAPKGXWVK2P1SZR1U2MS/Screen+Shot+2020-12-16+at+5.29.20+PM.png General Blog - Does SARS-CoV-2 reverse transcribe and integrate into our genome? V’kovski P, Kratzel A, Steiner S, Stalder H, Thiel V. 2020. Coronavirus biology and replication: implications for SARS-CoV-2. Nat Rev Microbiol. doi:10.1038/s41579-020-00468-6. http://dx.doi.org/10.1038/s41579-020-00468-6. Figure 4 which demonstrates that coronavirus RNA replication is discontinuous; in other words, the RNA-dependent RNA polymerase can pause and then pick up other sequences (that’s called template switching)- which would result in… a chimeric sequence. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1608156706348-TZ4S99JAMOQMKUP3ZYY3/image-asset.png General Blog - Does SARS-CoV-2 reverse transcribe and integrate into our genome? Hwang B, Lee JH, Bang D. 2018. Single-cell RNA sequencing technologies and bioinformatics pipelines. Exp Mol Med. 50(8):96. Figure 1G. In essence, after isolating your cells, you would have a bead which has primers attached to it for a reverse transcription reaction. You then break open the cell to release its RNA transcripts which stick to the primers that have complementary sequences. Then you run a reverse transcription reaction. Here’s the key point: the reverse transcription will do template switching: it will start making a DNA on one strand, pause, and then wander onto another strand. Then you have the bioinformatics work of figuring out which partial sequences are from which gene. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1608098891499-37GM5SLT1Z3JW9386AJY/Screen+Shot+2020-12-16+at+12.26.22+AM.png General Blog - Does SARS-CoV-2 reverse transcribe and integrate into our genome? https://www.deplatformdisease.com/blog/moderna-vrbpac-data-summary monthly 0.5 2020-12-16 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1608062810146-QJ7GWIC0WMJWOLWW337F/Screen+Shot+2020-12-15+at+3.06.42+PM.png General Blog - Moderna VRBPAC Data Summary https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1608060396563-3RCVZOAPSFE7XYDZWU29/Screen+Shot+2020-12-15+at+2.26.20+PM.png General Blog - Moderna VRBPAC Data Summary https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1608064375897-GAHD19786FBOOT7JSC20/image-asset.png General Blog - Moderna VRBPAC Data Summary General scheme of Moderna’s trial. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1608059930560-ZZHKWM1XJB28GD1EOY3Q/Screen+Shot+2020-12-15+at+2.16.15+PM.png General Blog - Moderna VRBPAC Data Summary https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1608061151557-NXTKI8GZDLEAFYVSJ9GQ/image-asset.png General Blog - Moderna VRBPAC Data Summary Widge AT, Rouphael NG, Jackson LA, Anderson EJ, Roberts PC, Makhene M, Chappell JD, Denison MR, Stevens LJ, Pruijssers AJ, et al. 2020. Durability of responses after SARS-CoV-2 mRNA-1273 vaccination. N Engl J Med.(NEJMc2032195). doi:10.1056/NEJMc2032195. http://dx.doi.org/10.1056/NEJMc2032195. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1608055035010-WRIJ3SI5QE8QT9UXPZNJ/Screen+Shot+2020-12-15+at+12.56.55+PM.png General Blog - Moderna VRBPAC Data Summary https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1608074591663-WB24TILSC8PF6LG46PRX/Screen+Shot+2020-12-15+at+6.22.53+PM.png General Blog - Moderna VRBPAC Data Summary https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1608064426492-J6AOLO2X5711DMM2PMKL/Screen+Shot+2020-12-15+at+2.06.35+PM.png General Blog - Moderna VRBPAC Data Summary https://www.deplatformdisease.com/blog/corrigendum monthly 0.5 2021-02-22 https://www.deplatformdisease.com/blog/why-some-vaccines-are-more-uncomfortable-than-others monthly 0.5 2020-12-16 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1607714168743-05YII3IVDQ1IXWVF2OTZ/image-asset.png General Blog - Why are some vaccines more uncomfortable than others? Hervé C, Laupèze B, Del Giudice G, Didierlaurent AM, Tavares Da Silva F. 2019. The how’s and what’s of vaccine reactogenicity. NPJ Vaccines. 4(1):39. Figure 2; When you get a vaccine, it triggers inflammation at the injection site, which is characterized by 4 things: heat, pain, swelling, and redness (depending on how deep the injection is you might not see all of these). These help to recruit the machinery of the immune system to engage productively with the immune response. The stimuli are noxious however, and thus activate nociceptors (pain receptors) which send signals of pain. At the same time, inflammatory mediators at the vaccination site produce pro-inflammatory cytokines that travel to the liver to make so-called acute phase proteins, which enhance the immune response. The pro-inflammatory cytokines help with a productive immune response as well, but can also induce fever through signaling with the brain. Hence, it’s very hard to disentangle the efficacy of a vaccine from its reactogenicity. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1607729712883-04XZSIFSRY7KU4D2RO3Y/Screen+Shot+2020-12-11+at+6.35.05+PM.png General Blog - Why are some vaccines more uncomfortable than others? Irwin MR. 2019. Sleep and inflammation: partners in sickness and in health. Nat Rev Immunol. 19(11):702–715. Figure 1: Sleep and the immune response have a complex relationship; in general the inflammatory mediators produced by immune response enhance slow-wave sleep (SWS), the deepest phase of sleep, and reduce REM (rapid eye movement) sleep (when we dream), which results in more efficient sleep and increased sleep time. This is shown to enhance antiviral responses and promote the survival of the host in the context of infection. https://www.deplatformdisease.com/blog/safety-concerns-about-the-pfizer-vaccine-anaphylactoid-reactions-and-the-pre-licensure-data monthly 0.5 2020-12-12 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1607543513398-SFCV65MLZVZNXF0QHPX2/image-asset.png General Blog - Safety Concerns About the Pfizer Vaccine: The Pre-Licensure Data and Anaphylactoid Reactions in the UK https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1607552733367-9Y2CMQN345JK4UJKP314/image-asset.png General Blog - Safety Concerns About the Pfizer Vaccine: The Pre-Licensure Data and Anaphylactoid Reactions in the UK A list of excipients (inactive ingredients) in the Pfizer-BioNTech COVID-19 vaccine. https://www.deplatformdisease.com/blog/will-the-covid-19-vaccines-be-safe-for-immunocompromised-patients monthly 0.5 2020-12-10 https://www.deplatformdisease.com/blog/what-is-antibody-dependent-enhancement-ade monthly 0.5 2020-12-10 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1607118937327-704UTHABOBBACXN80WEM/Screen+Shot+2020-12-04+at+4.55.13+PM.png General Blog - What is Antibody-Dependent Enhancement (ADE)? Lu, L. L., Suscovich, T. J., Fortune, S. M., & Alter, G. (2018). Beyond binding: antibody effector functions in infectious diseases. Nature Reviews. Immunology, 18(1), 46–61. Figure 3, summarizing the different effector functions of antibodies. Antibodies do bind and neutralize viruses and toxins, but they can also do many other things. For instance, they prevent biofilm formation (IgA antibodies, which are very abundant at mucosal surfaces, are particularly good at this). They can also stimulate release of chemokines- small proteins that direct cells to the source of the chemokines. Furthermore they can activate other cells of the immune system, like neutrophils, macrophages, and NK cells. In viral infection, antibody-dependent cellular cytotoxicity (ADCC) can be very important for killing infected cells, and in particular, afucosylated antibodies (antibodies without fucose sugars on them) are very good at this. IgG antibodies are also very important activators of complement (IgM can also do this but to a lesser extent). Fc receptors on the surfaces of cells can sense antibodies and their signaling can change the behavior of cells. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1607131767555-DFJHV5YPLL57G2J5SWZ8/image-asset.png General Blog - What is Antibody-Dependent Enhancement (ADE)? Arvin, A. M., Fink, K., Schmid, M. A., Cathcart, A., Spreafico, R., Havenar-Daughton, C., … Virgin, H. W. (2020). A perspective on potential antibody-dependent enhancement of SARS-CoV-2. Nature, 584(7821), 353–363. Table 1, describing the value and limitations of studies attempting to characterize ADE. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1607109374837-4E5UHWL33VVPT9B0GPZV/image-asset.png General Blog - What is Antibody-Dependent Enhancement (ADE)? ROBERT R. RICH MD, THOMAS A. FLEISHER MD, WILLIAM T. SHEARER MD, PhD, HARRY W. SCHROEDER, JR. MD, PhD, ANTHONY J. FREW MD, FRCP, CORNELIA M. WEYAND. (2018). Clinical immunology: Principles and practice (5th ed.). London, England: Elsevier Health Sciences. Figure 7.6 which demonstrates the standard way we think of immunity. There is sometimes a distinction made between memory B cells and plasma cells in that memory B cells provide reactive memory because on challenge with an antigen, they undergo rapid expansion to escalate production of protective antibodies, whereas long-lived plasma cells continuously secrete antibody levels without significant changes to their numbers even on challenge, and thus are said to provide protective memory. Both types of immunity do protect the host, and the extent to which one or the other is protective depends on the individual. This distinction can be important because memory B cells express a protein called CD20 that isn’t found on plasma cells, and in some disease states, anti-CD20 antibodies can be administered to kill off memory B cells that might be pathologic, but this leaves behind the plasma cells, which can be important if the plasma cells are the ones driving the disease pathology. In addition, with each exposure to the antigen, the antibodies become more refined and bind with greater affinity (and avidity), which is known as affinity maturation. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1607187123402-XT8DZ0Z066OAWY4HA2JV/Screen+Shot+2020-12-05+at+11.51.56+AM.png General Blog - What is Antibody-Dependent Enhancement (ADE)? Su S, Du L, Jiang S. 2020. Learning from the past: development of safe and effective COVID-19 vaccines. Nat Rev Microbiol. doi:10.1038/s41579-020-00462-y. http://dx.doi.org/10.1038/s41579-020-00462-y. Box 1 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1607100872232-20L96QU3N4Z05WZJEAEO/Screen+Shot+2020-12-04+at+11.54.27+AM.png General Blog - What is Antibody-Dependent Enhancement (ADE)? Elong Ngono, A., & Shresta, S. (2018). Immune response to dengue and Zika. Annual Review of Immunology, 36(1), 279–308. Figure 3b summarizing the possible outcomes of dengue infection. The initial infection can be mild or produce no disease at all. Then, depending on the quality of antibodies generated and the secondary infection, there can be severe dengue or no disease. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1607131666871-2SGXRVWK61KU52KERWQ8/Screen+Shot+2020-12-04+at+8.27.40+PM.png General Blog - What is Antibody-Dependent Enhancement (ADE)? Arvin, A. M., Fink, K., Schmid, M. A., Cathcart, A., Spreafico, R., Havenar-Daughton, C., … Virgin, H. W. (2020). A perspective on potential antibody-dependent enhancement of SARS-CoV-2. Nature, 584(7821), 353–363. Figure 2, summarizing potential mechanisms by which ADE might occur. Note that these are also normal physiological actions of antibodies, and it is not clear what drives pathogenic responses and what drives protective responses. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1607132957290-MZ5RR2OBCCMKV0NMG6F3/image-asset.png General Blog - What is Antibody-Dependent Enhancement (ADE)? Su S, Du L, Jiang S. 2020. Learning from the past: development of safe and effective COVID-19 vaccines. Nat Rev Microbiol. doi:10.1038/s41579-020-00462-y. http://dx.doi.org/10.1038/s41579-020-00462-y. Figure 2, summarizing different mechanisms by which a vaccine can cause immunopathology. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1607183740160-0FRU5HADWYP2IKA4XY05/Screen+Shot+2020-12-05+at+10.55.21+AM.png General Blog - What is Antibody-Dependent Enhancement (ADE)? Openshaw PJM, Chiu C, Culley FJ, Johansson C. 2017. Protective and harmful immunity to RSV infection. Annu Rev Immunol. 35(1):501–532. Figure 2. RSV is a complex pathogen requiring many components of the immune system to work together effectively to clear it. Antibodies alone are insufficient. Neutralizing antibodies target the prefusion conformation of the RSV fusion protein (F) but this protein is metastable, and thus can conceal the protective epitopes from the antibodies, and face competition from other antibodies targeting non-protective, but immunodominant epitopes. Effective CD8 responses are important for clearing infected cells, as are NK cells. It seems that significant involvement of either eosinophils, or neutrophils results in immunopathology and does not benefit the host in viral clearance or survival. Some pathology also seems to result from uncontrolled viral replication, but most of it seems to be induced by the host’s overenthusiastic immune response and the inability of immunoregulatory mechanisms to suppress the response. Fundamentally, the respiratory tract is poorly tolerant of inflammation, and thus the balance of immunoregulatory and pathogen-clearing signals is a precarious balance. https://www.deplatformdisease.com/blog/how-many-people-have-to-get-a-sars-cov-2covid-19-vaccine-to-prevent-a-case-of-covid-19 monthly 0.5 2020-12-13 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1607898481048-7W62M8HW635UEQFXWHZV/Screen+Shot+2020-12-13+at+5.27.02+PM.png General Blog - How many people have to get a SARS-CoV-2/COVID-19 vaccine to prevent a case of COVID-19? And a few ancillary points. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606959258230-8JBJSY1OC67UXNT876TA/Screen+Shot+2020-12-02+at+8.33.55+PM.png General Blog - How many people have to get a SARS-CoV-2/COVID-19 vaccine to prevent a case of COVID-19? And a few ancillary points. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606944689514-A2JI4SWDUW2HBGHD8MUF/image-asset.png General Blog - How many people have to get a SARS-CoV-2/COVID-19 vaccine to prevent a case of COVID-19? And a few ancillary points. https://www.bmj.com/content/371/bmj.m4347/rr-4 https://www.deplatformdisease.com/blog/are-covid-19-vaccines-going-to-cause-infertility monthly 0.5 2020-12-16 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1607090564820-VCGCE93OW9FYFM0YQMHG/Screen+Shot+2020-12-04+at+9.02.28+AM.png General Blog - Are COVID-19 Vaccines Going To Cause Infertility? Faé KC, da Silva DD, Oshiro SE, Tanaka AC, Pomerantzeff PMA, Douay C, Charron D, Toubert A, Cunningham MW, Kalil J, et al. 2006. Mimicry in recognition of cardiac myosin peptides by heart-intralesional T cell clones from rheumatic heart disease. J Immunol. 176(9):5662–5670. Table VII https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1607018261301-DGX0AGFNAF36ACFK6XAK/Screen+Shot+2020-12-03+at+12.57.36+PM.png General Blog - Are COVID-19 Vaccines Going To Cause Infertility? Dupressoir, A., Lavialle, C., & Heidmann, T. (2012). From ancestral infectious retroviruses to bona fide cellular genes: role of the captured syncytins in placentation. Placenta, 33(9), 663–671. Figure 2b. The syncytin protein has a complementary receptor. As the virus infects the cell, the protein appears on the surface. If it makes contact with its receptor on another adjacent cell, the two cells fuse. Doing this successively many times produces a syncytium, like the syncytiotrophoblast, or skeletal or cardiac muscles. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1607022055293-AYWHPKFHTMVAY0G09BEA/Screen+Shot+2020-12-03+at+2.00.53+PM.png General Blog - Are COVID-19 Vaccines Going To Cause Infertility? https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1607021854681-RGD96QS5CBRVHDA10FUH/image-asset.png General Blog - Are COVID-19 Vaccines Going To Cause Infertility? The output of a BLAST search for the spike glycoprotein of SARS-CoV-2. Note that no human sequences align, but there is exceptional homology with many other SARS-CoV-2 isolates. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1607087318041-849EX7RF6N6VOMKMXVC5/Screen+Shot+2020-12-04+at+8.08.31+AM.png General Blog - Are COVID-19 Vaccines Going To Cause Infertility? https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1607018917209-DJR6B1ZH50SW5HQDNTXI/Screen+Shot+2020-12-03+at+1.08.31+PM.png General Blog - Are COVID-19 Vaccines Going To Cause Infertility? Dupressoir, A., Lavialle, C., & Heidmann, T. (2012). From ancestral infectious retroviruses to bona fide cellular genes: role of the captured syncytins in placentation. Placenta, 33(9), 663–671. Figure 3b, demonstrating the structure of the fetal vessels with the uterus in the placenta. The syncytiotrophoblast (SCT) is the outermost layer of the fetal villus, and exists as a true syncytium. SCTs make hormones that are important for fetal development, have direct contact with maternal blood and thus directly regulate the exchange of gas, nutrients, and waste, and serve as an important barrier against infection of the fetus. https://www.deplatformdisease.com/blog/covid-19-and-influenza-are-very-different monthly 0.5 2020-12-06 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606766835243-T2JYWBLJBKR54YTLPUXY/Screen+Shot+2020-11-30+at+3.06.57+PM.png General Blog - COVID-19 and influenza are very different Rydyznski Moderbacher C, Ramirez SI, Dan JM, et al. Antigen-specific adaptive immunity to SARS-CoV-2 in acute COVID-19 and associations with age and disease severity. Cell. Published online 2020. doi:10.1016/j.cell.2020.09.038 Graphical Abstract. The immune response to SARS-CoV-2 requires a careful collaboration along cellular and humoral immunity, and patients who fare the best in COVID-19 are those who have productive responses along all of these. With age, impairment of each of these arms occurs to varying degrees, complicating recovery. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606487750558-CRUT25HDR1KRXYC4Q0WO/image-asset.png General Blog - COVID-19 and influenza are very different Krammer, F., Smith, G.J.D., Fouchier, R.A.M. et al. Influenza. Nat Rev Dis Primers 4, 3 (2018). https://doi.org/10.1038/s41572-018-0002-y Figure 3, demonstrating the emergence of novel influenza viruses into human populations across species. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606434635309-D32AKA3ICUMLXAIF3R5Q/Screen+Shot+2020-11-26+at+6.50.29+PM.png General Blog - COVID-19 and influenza are very different Flint J, Racaniello VR, Rall GF, Skalka AM. Principles of Virology, Fourth Edition. ASM Press; 2015. Figure 6.27 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606768415341-LUDMW3324C69RD5JJQ74/Screen+Shot+2020-11-30+at+3.33.14+PM.png General Blog - COVID-19 and influenza are very different Baloxavir for Uncomplicated Influenza | NEJM. The mechanism of action of Baloxavir. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606755237233-PGJYUXXCUVPZP6RYSTS0/Screen+Shot+2020-11-30+at+11.53.51+AM.png General Blog - COVID-19 and influenza are very different Krammer F. The human antibody response to influenza A virus infection and vaccination. Nat Rev Immunol. 2019;19(6):383-397. Figure 2, demonstrating models of original antigenic sin for influenza. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606418782160-7KOIWTX2KWYQDORVVQA7/image-asset.png General Blog - COVID-19 and influenza are very different Mortality risk of COVID-19 - statistics and research. Ourworldindata.org. https://ourworldindata.org/mortality-risk-covid; You will note that the rise in risk of death is essentially monotonic and increases with age in an exponential manner. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606786208185-GN4RE1KJKE2E7CW3V02J/Screen+Shot+2020-11-30+at+8.29.48+PM.png General Blog - COVID-19 and influenza are very different Iwasaki A, Pillai PS. Innate immunity to influenza virus infection. Nat Rev Immunol. 2014;14(5):315-328 Table 2, summarizing genetic factors which are important to the host response against influenza. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606413688203-XS9FAJEHUUR9AC7ERLGV/image-asset.png General Blog - COVID-19 and influenza are very different Hartenian E, Nandakumar D, Lari A, Ly M, Tucker JM, Glaunsinger BA. The molecular virology of coronaviruses. The journal of biological chemistry. 2020;295(37):12910–12934 Figure 1, summarizing the replication cycle of coronaviruses like SARS-CoV-2. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606487012803-TLVJ7YX20YIGQ3GLB15T/image-asset.png General Blog - COVID-19 and influenza are very different Streicker DG, Gilbert AT. Contextualizing bats as viral reservoirs. Science (New York, N.Y.). 2020;370(6513):172–173. Figure 1 demonstrating the emergence of novel coronaviruses. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606414921190-A5IIIDYCDKWNU6YBT48Z/image-asset.png General Blog - COVID-19 and influenza are very different Hutchinson EC. Influenza Virus. Trends in microbiology. 2018. http://dx.doi.org/10.1016/j.tim.2018.05.013. doi:10.1016/j.tim.2018.05.013 This figure shows the standard replication cycle of influenza viruses. If you’re not sure what you’re looking for, the differences between it and the coronaviruses replication cycle are not obvious, so please refer to the text. One thing worth noting: influenza viruses do have a filamentous form shown in this figure (the long one) which differs from the round depiction they are often represented as having. The filamentous form may be more important in the causation of the disease than the spherical one, though it is also more fragile and thus harder to isolate in culture. This figure also shows the virus in a bacilliform shape (slightly elongated rounded rectangle basically), which also occur in addition to the spherical. Coronaviruses by contrast generally occur in just one spherical shape. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606415145846-9LCYO0KD9MP2C905DNIZ/image-asset.png General Blog - COVID-19 and influenza are very different Influenza, the virus responsible for the pestilence that I thought would be my end. Influenza A and B viruses are more similar to each other than to influenza C (and D; not shown as they are relatively newly discovered) viruses. Key things to note here are that C viruses have 7 segments of RNA while A and B both have 8. Influenza A viruses are generally regarded as zoonoses (they come from animals), while B and C viruses are generally considered to be restricted to humans (though there have been documented cases of influenza B virus transmission between humans and harbor seals). C viruses also integrate the function of the hemagluttinin (HA) and neuraminidase (NA) into a single protein called Hemagluttinin-esterase fusion protein (HEF). A and B viruses also bear additional accessory proteins: PA-x (which seems to have a role in encouraging viral growth and suppressing innate immune responses) and PB1-F2 (which induces cell death). From Cherry J, Demmler-Harrison GJ, Kaplan SL, Steinbach WJ, Hotez PJ. Feigin and cherry’s textbook of pediatric infectious diseases: 2-Volume set. 8th ed. Philadelphia, PA: Elsevier - Health Sciences Division; 2018. Figure 178.3 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606766998361-XIC8UTTWZL8S1GUFNH21/image-asset.png General Blog - COVID-19 and influenza are very different Iwasaki A, Pillai PS. Innate immunity to influenza virus infection. Nat Rev Immunol. 2014;14(5):315-328 Figure 2, summarizing innate sensing mechanisms of the host in response to influenza infection. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606835069218-Q32405N1EOKRW6OG5BGK/Screen+Shot+2020-12-01+at+10.01.20+AM.png General Blog - COVID-19 and influenza are very different Couzin-Frankel J. The long haul. Science. 2020;369(6504):614-617. COVID-19 causes persistent symptoms in many of the patients who recover which can be psychologically devastating in addition to the resultant physical disability. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606416138192-X21I4DS46DB5AFBC5I23/Screen+Shot+2020-11-26+at+1.42.15+PM.png General Blog - COVID-19 and influenza are very different From Cherry J, Demmler-Harrison GJ, Kaplan SL, Steinbach WJ, Hotez PJ. Feigin and cherry’s textbook of pediatric infectious diseases: 2-Volume set. 8th ed. Philadelphia, PA: Elsevier - Health Sciences Division; 2018. Table 178-2; You can cross-correlate my experience with what’s mentioned here for manifestations in children, which will tell you that the case I had was fairly typical. I had all the common symptoms, didn’t get the rare ones, and had a few uncommon ones. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606587981813-5NLQ60IYUC8IJSSZ24NR/Screen+Shot+2020-11-28+at+1.25.33+PM.png General Blog - COVID-19 and influenza are very different Solomon DA, Sherman AC, Kanjilal S. Influenza in the COVID-19 era. JAMA: the journal of the American Medical Association. 2020. http://dx.doi.org/10.1001/jama.2020.14661. doi:10.1001/jama.2020.14661 Table 1 https://www.deplatformdisease.com/blog/vaccines-and-autoimmune-disease monthly 0.5 2022-10-18 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606692874770-UYEF3YBOA5TOUE3QADTC/Screen+Shot+2020-11-29+at+6.34.27+PM.png General Blog - Vaccines and Autoimmune Disease ElTanbouly MA, Noelle RJ. Rethinking peripheral T cell tolerance: checkpoints across a T cell’s journey. Nat Rev Immunol. Published online 2020. doi:10.1038/s41577-020-00454-2 Figure 1, demonstrating checkpoint mechanisms against autoimmunity in the lifespan of a T cell. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606676862798-VO6FR8LTYS1E10YOWNKY/Screen+Shot+2020-11-29+at+2.06.55+PM.png General Blog - Vaccines and Autoimmune Disease Husebye, E. S., Anderson, M. S., & Kämpe, O. (2018). Autoimmune Polyendocrine Syndromes. The New England Journal of Medicine, 378(12), 1132–1141. Figure 1, demonstrating the manifestations of autoimmune polyendocrine syndromes. APS-1 results entirely from a near-total failure of central tolerance mechanisms. IPEX syndrome, which is more severe in nature, results from a near-total failure of peripheral tolerance mechanisms. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606679039855-XGKKL18YAGRII5TLHVFX/Screen+Shot+2020-11-29+at+2.43.40+PM.png General Blog - Vaccines and Autoimmune Disease Rosenblum MD, Remedios KA, Abbas AK. Mechanisms of human autoimmunity. J Clin Invest. 2015;125(6):2228-2233 Figure 2: Autoimmune disease does not just happen. It requires a complex series of risk factors and chance events. Firstly, there needs to be a genetic susceptibility to the autoimmunity in question, for instance, as in APS-1, absent functional AIRE. There then needs to be some kind of environmental trigger to take extant autoreactive cells and precipitate an immune response from them, such as an infection. Finally, peripheral tolerance mechanisms have to fail to suppress the resultant tissue damage. This is not something that any arrant immune response is capable of doing. In fact, typically when infections do precipitate autoimmune disease it is due to the presence of structurally similar antigens (molecular mimicry). https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606681359650-JDSCF65PJ34IIK3GLWQN/Screen+Shot+2020-11-29+at+3.22.37+PM.png General Blog - Vaccines and Autoimmune Disease Murphy K, Weaver C. Janeway’s Immunobiology. 9th ed. CRC Press; 2016. Table 15.2, showing the numerous suppressive mechanisms that safeguard against autoimmunity. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606677838348-CUSEKQ6LK2YP6CD4GB8L/Screen+Shot+2020-11-29+at+2.23.56+PM.png General Blog - Vaccines and Autoimmune Disease Rose NR, Mackay IR. The Autoimmune Diseases, 6th Edition.; 2020. Figure 5.2, summarizing central tolerance in T cells. The fate of a T cell depends on how strongly it is able to bind to presented antigen in the thymus (avidity). Tissue-restricted antigens are presented such that T cells are assessed for responsiveness. The absence of a response from a T cell indicates that T cell is incapable of contributing to host defense, and thus does not receive survival signals (death by neglect). Cells that are slightly responsive to self-antigen can be valuable in host defense, and thus are selected for, which is called positive selection. Cells that respond somewhat strongly undergo functional deviation to become T regulatory cells that suppress immune responses on encounter with that antigen (this is known as agonist selection). If cells respond even more strongly than this, they are likely to produce autoimmune disease if allowed to exit from the thymus and are killed (clonal deletion). Central tolerance results in the death of more than 95% of T cells that undergo it. The key point here is: T cells have to fall into a goldilocks zone with how well they recognize antigen to even be able to survive, and they still get disciplined if they don’t do it well. https://www.deplatformdisease.com/blog/the-vaccines-for-sars-cov-2covid-19-werent-rushed monthly 0.5 2020-12-10 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606513717490-9FOE5S7PM183LMO34HXB/Screen+Shot+2020-11-27+at+4.48.14+PM.png General Blog - The vaccines for SARS-CoV-2/COVID-19 weren’t rushed The timeline of approval for some vaccines in routine use. Plotkin SA, Orenstein W, Offit DPA, Edwards KM. 2017. Plotkin’s Vaccines. 7th ed. Elsevier Table 4.3 https://www.deplatformdisease.com/blog/covid-19-vaccines-are-not-going-to-give-you-covid-19 monthly 0.5 2020-12-16 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606922638374-WUHEDTQSC3P7MGXUIBPI/Screen+Shot+2020-12-02+at+10.22.47+AM.png General Blog - COVID-19 vaccines are not going to give you COVID-19 Stock photos of vaccine receipt from SELF. Available here: https://www.flickr.com/photos/selfmagazine/48545839516/in/album-72157710332198661/ https://www.deplatformdisease.com/blog/no-really-mrna-vaccines-are-not-going-to-affect-your-dna monthly 0.5 2020-12-10 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606187959716-K0FDE5NKLJ7FID8FCLNE/Screen+Shot+2020-11-23+at+10.18.43+PM.png General Blog - No, Really, mRNA Vaccines Are Not Going To Affect Your DNA Flint S, Racaniello V, Rall G, Skalka A, Enquist L. Principles of virology. Washington, DC: ASM Press; 2015. Figure 5.23C which shows the nuclear import cycle with influenza ribonucleoproteins as an example. Nucleear localization signals are recognized by importin-α which then recruits importin-β which recruits a small GTPase called Ran. When binding GDP, Ran is able to transport the RNP across the nuclear pore complex. The complex of importins and Ran will then dissociate, and a guanine nucleotide exchange factor will exchange GDP for GTP, that allows Ran-GTP to be exported out of the nucleus. RanGAP-1 or RanBPI, 2 can then catalyze hydrolysis of GTP to GDP which allows Ran to bind another importin-β to initiate the import cycle once more. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606235040229-E4IIRX6JTXUCLF3JZ5QK/Screen+Shot+2020-11-24+at+9.29.07+AM.png General Blog - No, Really, mRNA Vaccines Are Not Going To Affect Your DNA Zhang Q, Kim N-K, Feigon J. Architecture of human telomerase RNA. Proceedings of the National Academy of Sciences of the United States of America. 2011;108(51):20325–20332. Figure 1 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606237076587-N0ZFYNWKVJZF31SZJ64J/Screen+Shot+2020-11-24+at+11.57.52+AM.png General Blog - No, Really, mRNA Vaccines Are Not Going To Affect Your DNA Hartwell L, Goldberg M, Fischer J, Hood L. Genetics. 6th ed. New York: McGraw Hill; 2018. Figure 12.20 showing the mechanism by which telomerase produces the telomere. the RNA primer https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606369596663-GTN6S4CEQMWRD0ATTO21/Screen+Shot+2020-11-26+at+12.46.11+AM.png General Blog - No, Really, mRNA Vaccines Are Not Going To Affect Your DNA Lodish H, Berk A, Kaiser C, Krieger M, Bretscher A, Ploegh H, Amon A, Martin K. Molecular cell biology. 8th ed. New York: W.H. Freeman; 2016. Figure 13-37B which demonstrates the export of mRNA from the nucleus. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606187220730-EEGPFZMVW1RC7WL7AI24/Screen+Shot+2020-11-23+at+10.06.55+PM.png General Blog - No, Really, mRNA Vaccines Are Not Going To Affect Your DNA Lodish H, Berk A, Kaiser C, Krieger M, Bretscher A, Ploegh H, Amon A, Martin K. Molecular cell biology. 8th ed. New York: W.H. Freeman; 2016. Figure 5-1 This figure is useful because you can clearly see the two compartments we care about: the nucleus, which houses almost all of the DNA (exception discussed), and the cytosol, which is where translation happens. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606180780641-X4KHZR8PBIKCC2GAEJQ5/Screen+Shot+2020-11-23+at+8.19.36+PM.png General Blog - No, Really, mRNA Vaccines Are Not Going To Affect Your DNA Flint S, Racaniello V, Rall G, Skalka A, Enquist L. Principles of virology. Washington, DC: ASM Press; 2015. Figure 7.2 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606235139617-QHO4TL3OF655FT07904F/Screen+Shot+2020-11-24+at+11.25.35+AM.png General Blog - No, Really, mRNA Vaccines Are Not Going To Affect Your DNA Linares-Fernández S, Lacroix C, Exposito J-Y, Verrier B. Tailoring mRNA vaccine to balance innate/adaptive immune response. Trends in molecular medicine. 2020;26(3):311–323. Figure 2 The basic organization of an mRNA vaccine’s sequence https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1606153924605-WEHFFZG8XIF0U0HRSZ1D/Screen+Shot+2020-11-23+at+12.51.47+PM.png General Blog - No, Really, mRNA Vaccines Are Not Going To Affect Your DNA Hartwell L, Goldberg M, Fischer J, Hood L. Genetics. 6th ed. New York: McGraw Hill; 2018. Table 13-2 https://www.deplatformdisease.com/blog/vaccine-efficacy-how-does-it-work monthly 0.5 2020-12-13 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1605638295376-MCX691LDH6A6COHQWQTC/Screen+Shot+2020-11-17+at+1.38.11+PM.png General Blog - SARS-CoV-2/COVID-19: How can we tell whether a vaccine works? Deaths in the Gardasil vaccine trials. See page 8. Many methods exist to determine whether or not there is a causal relationship between an adverse event and the pharmaceutical in question. Broadly, there are those based on expert opinion, algorithms, and probabilistic methods. There is a good discussion here, but it is paywalled. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1605560588652-4UEWE4KN96WSPB03BJ6U/Screen+Shot+2020-11-16+at+4.03.06+PM.png General Blog - SARS-CoV-2/COVID-19: How can we tell whether a vaccine works? Vaccine effectiveness is defined with respect to a given phenomenon. For instance, vaccines can (rarely) protect against infection entirely (see text for details), but measuring this properly is cumbersome and this is not necessary for a successful campaign. With bacteria, vaccines can have some protection against colonization of the pathogen at the relevant anatomical site. Some vaccines are unable to completely shield from disease but can prevent the worst outcomes. In addition to this, vaccines confer protection beyond the vaccinee (see text for details). Halloran M, Longini I, Struchiner C. Design and Analysis of Vaccine Studies. Springer Science; 2010. Table 2.1 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1605746359967-MQMHH8LMB0A7745YN4I3/Screen+Shot+2020-11-18+at+7.39.15+PM.png General Blog - SARS-CoV-2/COVID-19: How can we tell whether a vaccine works? https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1605560705219-NZE9JX45SX4B2TT2A4QG/Screen+Shot+2020-11-16+at+4.05.02+PM.png General Blog - SARS-CoV-2/COVID-19: How can we tell whether a vaccine works? N. E. Dean, P.-S. Gsell, R. Brookmeyer, V. De Gruttola, C. A. Donnelly, M. E. Halloran, M. Jasseh, M. Nason, X. Riveros, C. H. Watson, A. M. Henao-Restrepo, I. M. Longini, Design of vaccine efficacy trials during public health emergencies. Sci. Transl. Med. 11, eaat0360 (2019). https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1607898440187-F967DFX89O2O0MD3KOL0/Screen+Shot+2020-12-02+at+5.15.28+PM.png General Blog - SARS-CoV-2/COVID-19: How can we tell whether a vaccine works? https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1605743300336-ZSWCBLY8LCGJQRMQF0IK/Screen+Shot+2020-11-18+at+6.47.58+PM.png General Blog - SARS-CoV-2/COVID-19: How can we tell whether a vaccine works? O'neill R. On sample sizes to estimate the protective efficacy of a vaccine. Statistics in Medicine. 1988;7(12):1279-1288. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1605565741496-6MBCI6JJHZVJM570PV4J/Screen+Shot+2020-11-16+at+5.28.55+PM.png General Blog - SARS-CoV-2/COVID-19: How can we tell whether a vaccine works? DESIGN OF VACCINE EFFICACY TRIALS TO BE USED DURING PUBLIC HEALTH EMERGENCIES – POINTS OF CONSIDERATIONS AND KEY PRINCIPLES. Who.int. Figure 2 https://www.deplatformdisease.com/blog/whats-in-a-vaccine monthly 0.5 2020-12-06 https://www.deplatformdisease.com/blog/mrna-vaccines-and-covid-19 monthly 0.5 2020-12-08 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604199409432-51JY3YYYMCDS8LH6MG3X/image-asset.png General Blog - mRNA Vaccines and COVID-19 mRNA decay pathways https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604199906404-X6LAPUVY8GCJUKM4TXJ2/Screen+Shot+2020-10-31+at+11.04.56+PM.png General Blog - mRNA Vaccines and COVID-19 An integrated look at mRNA vaccination via injection. The mRNA vaccines will be delivered inside lipid nanoparticles that enter the cells and be taken up by antigen presenting cells like dendritic cells. There the mRNA will induce production of the encoded antigen and its processing to activate the antigen-presenting cells. The antigen-presenting cells will go on to activate T cells, especially T follicular helper cells, inside the nearest lymph node to induce a T cell response. B cells will be activated by the T follicular helper cells to make antibodies. Figure 3 from https://www.nature.com/articles/nrd.2017.243.pdf https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604198723375-Z8JF0VGJ2NGQ77335SL6/image-asset.png General Blog - mRNA Vaccines and COVID-19 The central dogma of molecular biology, as initially proposed. Since then we’ve discovered some more about it. The diagram shows that DNA is capable of replication from a DNA template, which is true, but RNA is also capable of this, though of course it needs RNA-dependent RNA polymerases, which some viruses do have. Some viruses, like HIV, also have an enzyme called reverse transcriptase which carries out reverse transcription- the synthesis of DNA from an RNA template (though this is not normally present in our cells). There is likely no reverse translation however. Some have argued that prions are an example of proteins that drive their own replication (thus being exceptions to the central dogma) but the mechanisms underlying this are not well understood. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1607376358359-NRUAD97WI8ZE2MI0WQI5/Screen+Shot+2020-12-07+at+4.25.33+PM.png General Blog - mRNA Vaccines and COVID-19 Janeway’s Immunobiology 9th Edition Figure 3.35; Interferons alpha and beta are the type 1 interferons which can be induced by virtually all cells in response to viral infection. Their presence triggers a suite of antiviral defenses. For one, they induce the production of chemokines (small proteins that direct blood cells to a particular area) that attract NK cells (the major innate immune cells responsible for antiviral immunity). They additionally produce proteins that suppress the production of proteins from viral RNA and activate antigen-presenting cells like dendritic cells and macrophages. Furthermore, they enhance the presentation of antigen dramatically (some viruses try to suppress this by reducing levels of MHC class I proteins- vehicles for presenting protein antigens; however missing MHC class 1 proteins trigger the killing action of natural killer cells). In general, interferons are extremely effective at controlling viral infections and for a virus to be able to cause an infection usually means it has to have some mechanism by which it can subvert the action of interferons. COVID-19 illustrates this well as in severe cases it seems that SARS-CoV-2 is able to delay the interferon response until it replicates to a level where it becomes insensitive to the interferons. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604199531449-X1G37SBX7EQ25FWQ8MPH/image-asset.png General Blog - mRNA Vaccines and COVID-19 Figure 1 from https://www.nature.com/articles/nrd.2017.243.pdf https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604199671431-O7R5V8HJID2082YBEYTT/Screen+Shot+2020-10-31+at+11.00.04+PM.png General Blog - mRNA Vaccines and COVID-19 The Baltimore Classifications groups viruses into 7 categories based on the nature of their genome. All 7 however must produce mRNA as part of their replication cycle. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1607375893903-43RK2PPSE3DHL9NSGW1Y/Screen+Shot+2020-12-07+at+4.17.56+PM.png General Blog - mRNA Vaccines and COVID-19 Alberts's Essential Cell Biology 5th Edition Figures 7-39 and 7-40 demonstrating the basics of the process of translation. Translation begins with an initiation stage, wherein a ribosome must scan the mRNA for a START codon, which also encodes the amino acid methionine. tRNAs are associated with amino acids, which undergo reactions called condensations to form peptides, and then proteins. The ribosome continues to travel along the mRNA adding new amino acids, until eventually, the mRNA STOP codon is found, at which point the ribosome will accept a release factor and dissassemble. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604199137747-APMELNTC0UB2B52JPCZW/image-asset.png General Blog - mRNA Vaccines and COVID-19 An overview of pre-mRNA processing from Voet’s Biochemistry 4th Edition Figure 31.51 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604199724087-VUXCMVCA2FARDUVLUYJR/Screen+Shot+2020-10-31+at+11.01.55+PM.png General Blog - mRNA Vaccines and COVID-19 How nucleic acids (DNA and RNA) can be distinguished as non-self or altered self to trigger immune responses. Broadly, a major factor is where the nucleic acid is located within the cell. DNA for example should not be found outside the nucleus or mitochondria of a cell. Another factor is the presence or absence of a cap on the mRNA (or whether it is the right cap), and whether or not the RNA is single stranded or not (all host RNA is single stranded; viruses may have double stranded RNA genomes). Source. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604199241027-JOQAWXGNZTFBMP4B064K/image-asset.png General Blog - mRNA Vaccines and COVID-19 Alternative spliceforms as illustrated by Voet’s Biochemistry 4th Edition Figure 31–65 https://www.deplatformdisease.com/blog/long-term-effects-of-covid-19-vaccines-should-you-be-worried monthly 0.5 2020-12-06 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604200229501-C2EDOF4H68BIP0TQH3XD/Screen+Shot+2020-10-31+at+11.10.22+PM.png General Blog - Long-Term Effects of COVID-19 Vaccines: Should You Be Worried? https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604200270629-J4HTU2MRW3QB44MS6XFB/Screen+Shot+2020-10-31+at+11.11.05+PM.png General Blog - Long-Term Effects of COVID-19 Vaccines: Should You Be Worried? This is a WHO guidance regarding the monitoring of adverse events. Source https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604200174683-BM10PKOGQ4E1VXLRFY8X/Screen+Shot+2020-10-31+at+11.09.25+PM.png General Blog - Long-Term Effects of COVID-19 Vaccines: Should You Be Worried? From Principles of Virology Volume 2 4th Edition Table 5.2 by Flint, Racaniello, Rall, Skalka, and Lehnquist https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604200110966-BAO8IIULYSKT1XB9O9DC/Screen+Shot+2020-10-31+at+11.08.22+PM.png General Blog - Long-Term Effects of COVID-19 Vaccines: Should You Be Worried? A summary of how varicella infection works. In short, the virus enters the body and establishes an infection in the cell and undergoes latency- a quiescent from where the virus persists in the form of DNA called an episome. Then, if the immune system undergoes some kind of suppression, the virus can reactivate inside neurons, causing shingles, or meningitis, or encephalitis. Because the vaccine is attenuated, this is much less likely to happen from it than from infection, which it reliably protects against, but it is nontheless a nonzero risk. Source. https://www.deplatformdisease.com/blog/covid-19-and-t-cell-immunity monthly 0.5 2020-12-23 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604255860518-YTZNR4SAV2NYQ8XYBYP3/Screen+Shot+2020-11-01+at+1.37.34+PM.png General Blog - COVID-19 and T Cell Immunity Some mechanisms by which a single T cell can end up recognizing multiple antigens through specificity to a specific epitope. Source https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604255776206-44RR552XTOXG0T166MCC/image-asset.png General Blog - COVID-19 and T Cell Immunity Janeway’s Immunobiology 9th Edition Figure 1.15 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604200558765-I4H6F9C4SGPBRQCVE0YP/Screen+Shot+2020-10-31+at+11.15.54+PM.png General Blog - COVID-19 and T Cell Immunity The basic principle of T cell function. T cells respond to a protein antigen presented by antigen-presenting cells, with each T cell clone being specific to a given region of that antigen. Source. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604200629884-KN9XVXS5CZ7S4ZDOJTBD/Screen+Shot+2020-10-31+at+11.17.06+PM.png General Blog - COVID-19 and T Cell Immunity Janeway’s Immunobiology 9th Edition Figure 1.14 https://www.deplatformdisease.com/blog/hydroxychloroquine-and-covid-19 monthly 0.5 2020-12-06 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604256533449-D5LFFMTLGGKQ8MEYU5CZ/image-asset.png General Blog - Hydroxychloroquine and COVID-19 Hydroxychloroquine in autoimmune/rheumatic disease, its major use. Source. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604256722141-XPNK4UR5YNTKMYUGTLCB/image-asset.png General Blog - Hydroxychloroquine and COVID-19 SARS-CoV-2 can enter cells either by way of endocytosis (in which case those virions may be, theoretically, vulnerable to agents like HCQ) or directly at the cell membrane, wherein HCQ cannot even theoretically have a decent effect. Cells expressing the protease TMPRSS2 will strongly favor the latter mode of entry. Source (amazing review) https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604256464980-VSJY3415B27IY4U9OF8V/Screen+Shot+2020-11-01+at+1.47.40+PM.png General Blog - Hydroxychloroquine and COVID-19 Link: https://twitter.com/stella_immanuel/status/1288266097842626560?s=20 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604256679534-XGHJDG4IYXMEV2VV1W7E/Screen+Shot+2020-11-01+at+1.51.16+PM.png General Blog - Hydroxychloroquine and COVID-19 Full thread viewable here: https://threadreaderapp.com/thread/1288871272261328902.html https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604256600288-0FV6335V96VF5E393G1T/Screen+Shot+2020-11-01+at+1.49.51+PM.png General Blog - Hydroxychloroquine and COVID-19 Virion endocytosis. https://www.deplatformdisease.com/blog/challenges-in-vaccine-design monthly 0.5 2020-12-06 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604257747167-Z4HOGL10ZIQQYG7V246J/image-asset.png General Blog - Challenges in Vaccine Design Source: Siegrist, C.-A., & Aspinall, R. (2009). B-cell responses to vaccination at the extremes of age. Nature Reviews Immunology, 9(3), 185–194. doi:10.1038/nri2508 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604258098745-DZ3NPIKOQ7URI8XMCZVV/image-asset.png General Blog - Challenges in Vaccine Design Table 1 from Akkina, R. (2013). Human immune responses and potential for vaccine assessment in humanized mice. Current Opinion in Immunology, 25(3), 403–409. doi:10.1016/j.coi.2013.03.009 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604257673079-K8O6YFI47DNKOLE9491K/image-asset.png General Blog - Challenges in Vaccine Design Source: Figure 38.3 Rich R. Clinical immunology. 5th ed. Elsevier; 2019. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604257932199-52IR1O1IYZI1GCL77WE5/Screen+Shot+2020-11-01+at+2.12.04+PM.png General Blog - Challenges in Vaccine Design Source: Table 2.10 Plotkin’s Vaccines 7th Edition https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604257029694-WPXFBU2SV42BSVRMADF2/image-asset.png General Blog - Challenges in Vaccine Design Dendritic cell licensing for cross-presentation and CD8 T cell activation (cross-priming). Source: Kurts, C., Robinson, B. W. S., & Knolle, P. A. (2010). Cross-priming in health and disease. Nature Reviews Immunology, 10(6), 403–414. doi:10.1038/nri2780 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604257100778-6YDIQBMASF1KPT1PGLCP/Screen+Shot+2020-11-01+at+1.58.16+PM.png General Blog - Challenges in Vaccine Design https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604257121734-9IL0PEKQD763Y2VSDCD1/Screen+Shot+2020-11-01+at+1.58.34+PM.png General Blog - Challenges in Vaccine Design https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604258043395-NIP7ODSRJUDLQ1R2RWTY/image-asset.png General Blog - Challenges in Vaccine Design Source: Janeway’s Immunobiology 9th Edition Figure 12.1 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604258154356-RMDUNGQKWFWC8GVY7YWW/image-asset.png General Blog - Challenges in Vaccine Design Source: Mathew, N. R., & Angeletti, D. (2020). Recombinant Influenza Vaccines: Saviors to Overcome Immunodominance. Frontiers in Immunology, 10. doi:10.3389/fimmu.2019.02997 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604257154874-RHAOIY0F3FN1WM10RMR9/Screen%2BShot%2B2020-11-01%2Bat%2B1.56.17%2BPM.jpg General Blog - Challenges in Vaccine Design Source: Janeway’s Immunobiology 9th Edition Figure 6.2 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604257507373-V1ADHWS4496WXIK3O90H/image-asset.png General Blog - Challenges in Vaccine Design Correlates of Vaccine-Induced Immunity. Source: Table 2.2 from Plotkin’s Vaccines 7th Edition https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604257785197-S706LKEXN6MHACP4IMOS/Screen+Shot+2020-11-01+at+2.09.38+PM.png General Blog - Challenges in Vaccine Design Strategies to deal with immunosenescence. Source: Rich R. Clinical immunology. 5th ed. Elsevier; 2019. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604258291612-UC7Z5NNFFZXMRFMGGRCQ/image-asset.png General Blog - Challenges in Vaccine Design Source: Figure 4 from Ruckwardt, T. J., Morabito, K. M., & Graham, B. S. (2019). Immunological Lessons from Respiratory Syncytial Virus Vaccine Development. Immunity, 51(3), 429–442. doi:10.1016/j.immuni.2019.08.007 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604258341924-SLQCJD56P3SZY4BZTZEW/image-asset.png General Blog - Challenges in Vaccine Design Summary of antibody-dependent enhancement. Source: Rothman, A. L. (2011). Immunity to dengue virus: a tale of original antigenic sin and tropical cytokine storms. Nature Reviews Immunology, 11(8), 532–543. doi:10.1038/nri3014 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604257558894-KD7SAYCZDN2J1URNYJ6Z/image-asset.png General Blog - Challenges in Vaccine Design Source: Table 2.5 from Plotkin’s Vaccines 7th Edition https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604257603674-9MJ3EF6MZ3V2VL5H6XYI/Screen+Shot+2020-11-01+at+2.06.36+PM.png General Blog - Challenges in Vaccine Design Source: Figure 2, Kollmann T, Marchant A, Way S. Vaccination strategies to enhance immunity in neonates. Science. 2020;368(6491):612–615. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604256873135-AYUHY26082FE7UWPU9FN/Screen+Shot+2020-11-01+at+1.54.29+PM.png General Blog - Challenges in Vaccine Design Source: Plotkin’s Vaccines 7th Edition Table 29.1 https://www.deplatformdisease.com/blog/aluminum-based-vaccine-adjuvants-much-ado-about-nothing monthly 0.5 2020-12-11 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604259110239-UQCR9IMKNTRBGMKYHX7L/image-asset.png General Blog - Aluminum-based vaccine adjuvants: much ado about nothing Source: Hawkes, D., Benhamu, J., Sidwell, T., Miles, R., & Dunlop, R. A. (2015). Revisiting adverse reactions to vaccines: A critical appraisal of Autoimmune Syndrome Induced by Adjuvants (ASIA). Journal of Autoimmunity, 59, 77–84. doi:10.1016/j.jaut.2015.02.005 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604258760683-P302CRXVHCH2HOO10F4E/image-asset.png General Blog - Aluminum-based vaccine adjuvants: much ado about nothing Guy classifies adjuvants as being type A, B, or C. Type A adjuvants activate TLRs (a type of pattern recognition receptor) which leads to activation of the antigen-presenting cell and serves to modulate co-stimulation (signal 2). Type B adjuvants assist with antigen presentation itself (signal 1). Type C adjuvants strictly affect co-stimulation. Of note, targeting signal 1 in isolation tends to be a poor strategy for enhancing vaccine efficacy, as co-stimulation tends to be the bottleneck for initiation of an immune response. Additionally, this review does not differentiate between signal 2 and signal 3, likely because it’s a bit older. Source: Guy B. The perfect mix: recent progress in adjuvant research. Nature Reviews Microbiology. 2007;5(7):396–397. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604258976528-6OV6UK3F73VCWQK0K2D8/Screen+Shot+2020-11-01+at+2.29.29+PM.png General Blog - Aluminum-based vaccine adjuvants: much ado about nothing Some of the mechanisms involved in aluminum-based adjuvant adjuvanticity. Some more mechanisms are present in this figure that merit discussion. In addition to causing pyroptosis with the release of IL-1β and IL-18, alum causes several other important responses. At the local level, signaling via alum results in the activation of phospholipase A2 (PLA2), which liberates arachidonic acid (AA), the precursor for lipid mediators of inflammation. COX-2 (cyclooxygenase-2) and mPGES-1 (microsomal prostaglandin E2 synthase-1) convert the arachidonic acid to prostaglandin E2, which is a lipid mediator of inflammation. Uric acid crystals inside the APC disrupt the lysosome and cause release of cathepsin B, which also serves to activate the NLRP3 inflammasome. It is also thought that because alum induces some local cell death it may cause release of double-stranded DNA. Some double-stranded DNA, specifically CpG DNA, is an alarmin- but it is rare in our genome and normally represents bacterial DNA. It binds the PRR known as TLR9, and this goes on to induce NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells), which is a critical transcription factor that induces the production of numerous pro-inflammatory genes essential for dealing with infection. However, TLR9 signaling requires the MyD88 adaptor protein, and adjuvant responses still occur in mice whose MyD88 has been knocked out genetically. At the same time, introducing DNase to the of vaccination does reduce adjuvant effect- however a subsequent study showed that these vaccines were contaminated with proteases which may serve to explain the blunted effect (as these would degrade the antigen). Further research into this mechanism is warranted. Source: Fierens, K., & Kool, M. (2012). The Mechanism of Adjuvanticity of Aluminium-Containing Formulas. Current Pharmaceutical Design, 18(16), 2305–2313. doi:10.2174/138161212800166004 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604258709867-369TBETOYT0MUFBCOI91/image-asset.png General Blog - Aluminum-based vaccine adjuvants: much ado about nothing Figure 9.22 Janeway’s Immunobiology 9th Edition https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604259163325-RA8CI3IC9RX9BS1BF3YK/image-asset.png General Blog - Aluminum-based vaccine adjuvants: much ado about nothing The “swiss cheese model” of autoimmune disease (specifically focusing on autoimmune thyroid disease). There are numerous things that have to occur concurrently for an autoimmune disease to develop in an individual. Source: Weetman, A. P. (2012). The Immunopathogenesis of Chronic Autoimmune Thyroiditis One Century after Hashimoto. European Thyroid Journal. doi:10.1159/000343834 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604259058783-EPZHKD7XQHOBL7OWRZZF/image-asset.png General Blog - Aluminum-based vaccine adjuvants: much ado about nothing The progression of adjuvant action of aluminum-based adjuvants on dendritic cells. Initially the co-precipitate of alum and adjuvant localize onto the membrane of a resting dendritic cell. Antigen begins to dissociate from the adjuvant and enters the cell, as cues from the cytoskeleton activate Syk which induces PI3K that serves to enhance phagocytosis. There is an upregulation of cell adhesion molecules like ICAM and LFA-1 on the dendritic cell to help it form secure associations with the CD4 T cell. At this point, the dendritic cell is activated and primed to activate CD4 T cells which will go on to activate B cells specific for the antigen. Source: Flach, T. L., Ng, G., Hari, A., Desrosiers, M. D., Zhang, P., Ward, S. M., … Shi, Y. (2011). Alum interaction with dendritic cell membrane lipids is essential for its adjuvanticity. Nature Medicine, 17(4), 479–487. doi:10.1038/nm.2306 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604258928604-1TVKPA8JNJ4JUJJRVKNE/image-asset.png General Blog - Aluminum-based vaccine adjuvants: much ado about nothing Mechanisms of NLRP3 inflammasome activation. In pyroptosis, the NLRP3 inflammasome is induced which results in activation of caspase 1 and ultimately leads to formation of a gasdermin-D pore that causes cell swelling and lysis that facilitates release of mature pro-inflammatory cytokines. Source: Shi, J., Gao, W., & Shao, F. (2017). Pyroptosis: Gasdermin-Mediated Programmed Necrotic Cell Death. Trends in Biochemical Sciences, 42(4), 245–254. doi:10.1016/j.tibs.2016.10.004 https://www.deplatformdisease.com/blog/sars-cov-2-and-the-lessons-we-have-to-learn-from-it monthly 0.5 2020-11-13 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604262503348-4PGJJCYFA7XXA55LW8EI/image-asset.png General Blog - SARS-CoV-2 and the lessons we have to learn from it. https://www.youtube.com/watch?v=eup3_i_5uaw&t=597s https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604259468162-REKI98K211PC29CHB6KW/Screen+Shot+2020-11-01+at+2.37.43+PM.png General Blog - SARS-CoV-2 and the lessons we have to learn from it. Mortality distribution for COVID-19. Courtesy of: https://virologydownunder.com/so-you-think-youve-about-to-be-in-a-pandemic/ https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604259874248-KX45KTAU6HRG0MB0Q83H/image-asset.png General Blog - SARS-CoV-2 and the lessons we have to learn from it. Proliferative and fibrotic phases in ARDS. Figure 3 from Thompson, B. T., Chambers, R. C., & Liu, K. D. (2017). Acute Respiratory Distress Syndrome. New England Journal of Medicine, 377(6), 562–572. doi:10.1056/nejmra1608077 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604262110537-YJRH17AF4DF6OXTO05F0/Screen+Shot+2020-11-01+at+3.21.09+PM.png General Blog - SARS-CoV-2 and the lessons we have to learn from it. https://blogs.cdc.gov/niosh-science-blog/2017/11/02/noshave/ https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604259512983-33WRPXTA13QUDV4TDNZR/Screen+Shot+2020-11-01+at+2.38.27+PM.png General Blog - SARS-CoV-2 and the lessons we have to learn from it. https://twitter.com/azbrodsky/status/1233842494993031169?s=20 There are people for whom getting SARS-CoV-2 will represent a very serious health threat- and they have to get it from someone. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604259560726-PJQQ87SYM8WGCI2GIG9Y/image-asset.png General Blog - SARS-CoV-2 and the lessons we have to learn from it. Figure 28.1 from Fields Virology 6th edition demonstrating the phylogeny of the Nidovirales order. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604259611006-H6LMGOKPUXJKPRJF2AEW/Screen+Shot+2020-11-01+at+2.39.53+PM.png General Blog - SARS-CoV-2 and the lessons we have to learn from it. Mouse hepatitis virus, a coronavirus that has been experimentally important because of its help in understanding the virology of the coronaviruses, especially with respect to viral replication. Figure 28.2 from Fields Virology 6th Edition. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604259815714-QGAICHGOVX14PXQ8RWGQ/image-asset.png General Blog - SARS-CoV-2 and the lessons we have to learn from it. The exudative phase of ARDS. The phenomenon seems to be largely orchestrated by alveolar macrophages which upon detecting inflammatory insult go on to release numerous pro-inflammatory cytokines resulting in the recruitment of neutrophils and CD4 T cells, which go on to amplify inflammation, a hallmark of which is vascular leakage to facilitate invasion by leukocytes and clear the threat to the host. This however, causes severe difficulties with gas exchange at affected alveoli resulting in hypoxemia and respiratory failure. Source: Figure 2 from Thompson, B. T., Chambers, R. C., & Liu, K. D. (2017). Acute Respiratory Distress Syndrome. New England Journal of Medicine, 377(6), 562–572. doi:10.1056/nejmra1608077 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604259765098-TQHJGY1KPQ1D0G8ZJ91R/image-asset.png General Blog - SARS-CoV-2 and the lessons we have to learn from it. https://els-jbs-prod-cdn.literatumonline.com/pb/assets/raw/Lancet/infographics/coronavirus/Coronavirus_MedianTimeline_Infographic-1580399120550.jpg https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604260004529-C58QTMETW1I3TOWHKYZP/image-asset.png General Blog - SARS-CoV-2 and the lessons we have to learn from it. https://www.thelancet.com/action/showPdf?pii=S2214-109X%2820%2930068-1 https://www.deplatformdisease.com/blog/life-in-the-time-of-covid-19-the-portrait-of-a-high-risk-patient monthly 0.5 2020-11-13 https://www.deplatformdisease.com/blog/the-many-myths-of-influenza monthly 0.5 2020-11-13 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604262666930-YTLZBNJLK2QT4SY7ALV6/Screen+Shot+2020-11-01+at+3.30.58+PM.png General Blog - The Many Myths Of Influenza The basic structure of an influenza virus. There is also a filamentous (rather than spherical) form. http://www.virology.ws/2009/04/30/structure-of-influenza-virus https://www.deplatformdisease.com/blog/the-th1-th2-model-and-vaccination monthly 0.5 2020-11-13 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604263710737-PC72I1A3LQUKDIV0WF71/image-asset.png General Blog - The Th1-Th2 Model and Vaccination Source: Janeway’s Immunobiology 9th Edition Figure 9.30 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604263547173-DKBON6KVGURYE78HEY5A/image-asset.png General Blog - The Th1-Th2 Model and Vaccination Source: Janeway’s Immunobiology 9th Edition Figure 13.20 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604263670828-LZZT0IFJXBBD8FZSGSLD/image-asset.png General Blog - The Th1-Th2 Model and Vaccination Source: Janeway Immunobiology 9th Edition Figure 13.20 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604263599013-MLM0XWH85L9G8EJT0WY2/Screen+Shot+2020-11-01+at+3.46.32+PM.png General Blog - The Th1-Th2 Model and Vaccination Source: https://www.nature.com/articles/nri.2017.106 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604263500773-GW4FZCEFMR0DQCRV8OF8/Screen+Shot+2020-11-01+at+3.44.12+PM.png General Blog - The Th1-Th2 Model and Vaccination The figure depicts just some of the cells of your immune system and their stem cell lineages and development. Suffice it to say, your immune system is very complex. T cells are the purple cells in the top half of the figure that come from the lymphoid progenitor cell. The details of this diagram are not essential for anyone reading this article to understand. I merely include the picture to show how vast and complex the immune system is (very). Source: Clinical Immunology 5th Edition by Rich et al Figure 2.1. https://www.deplatformdisease.com/blog/the-vaccine-study-that-anti-vaccine-activists-think-they-want monthly 0.5 2020-11-13 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604263846780-4ZQ0PGW6PM4N5DBI8OM5/image-asset.png General Blog - The Vaccine Study That Anti-Vaccine Activists Think They Want https://www.cdc.gov/vaccines/schedules/downloads/child/0-18yrs-child-combined-schedule.pdf https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604263931500-963KAA21LRECFC7AIEOM/Screen+Shot+2020-11-01+at+3.52.08+PM.png General Blog - The Vaccine Study That Anti-Vaccine Activists Think They Want Courtesy of https://thelogicofscience.com/2016/01/12/the-hierarchy-of-evidence-is-the-studys-design-robust/ https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604263888805-QAB97LASNKULSX6JYRK6/image-asset.png General Blog - The Vaccine Study That Anti-Vaccine Activists Think They Want From https://pediatrics.aappublications.org/content/pediatrics/111/3/674.full.pdf https://www.deplatformdisease.com/blog/herd-immunity-how-does-it-work monthly 0.5 2020-11-13 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604264259810-KU1Q96XK836PZFPC5RFX/image-asset.png General Blog - Herd Immunity: How Does It Work? Values used for R0 will vary considerably with the source; I simply averaged the ranges provided on Wikipedia. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604264046292-7EMR7B66DJ3EY416IXEK/Screen+Shot+2020-11-01+at+3.53.58+PM.png General Blog - Herd Immunity: How Does It Work? Source: Plotkin S, Orenstein W, Offit P, Edwards K. Plotkin’s Vaccines . 7th ed. Saint Louis: Elsevier; 2017. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604264105495-M7YI7TLDXOFWNCS7HAIG/Screen+Shot+2020-11-01+at+3.55.02+PM.png General Blog - Herd Immunity: How Does It Work? Source: Reference 2 https://www.deplatformdisease.com/blog/vaccine-classes-a-survey monthly 0.5 2020-11-13 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604264449953-Q5QGITMMZWRP6VDFYAFB/Screen+Shot+2020-11-01+at+4.00.46+PM.png General Blog - Vaccine Classes: A Survey https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604264702447-N6RUAKM80L0C7QQ8SW24/Screen+Shot+2020-11-01+at+4.04.56+PM.png General Blog - Vaccine Classes: A Survey https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604264604716-RXNDHMWSBF8SOIEZV8WZ/Screen+Shot+2020-11-01+at+4.03.15+PM.png General Blog - Vaccine Classes: A Survey https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604264486349-0ZAIGS91N7HGHO84JHEV/image-asset.png General Blog - Vaccine Classes: A Survey https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604264377432-0F2ASSH1Y3BQMID8XDFN/Screen+Shot+2020-11-01+at+3.59.29+PM.png General Blog - Vaccine Classes: A Survey Some concepts for an HIV vaccine candidate. Thus far, HIV has presented an insurmountable challenge in vaccinology, but progress is being made constantly. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604264411795-DVLCEVFAAYZ3MDCSPOGR/Screen+Shot+2020-11-01+at+4.00.09+PM.png General Blog - Vaccine Classes: A Survey https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604264527347-QFW34UOW6MQP53YY8NAQ/Screen+Shot+2020-11-01+at+4.01.59+PM.png General Blog - Vaccine Classes: A Survey https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604264672032-KVLWVK60YY162XR5SUAE/image-asset.png General Blog - Vaccine Classes: A Survey https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604264564649-OH362XB5KGKV29GX7295/image-asset.png General Blog - Vaccine Classes: A Survey https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604264640588-BYC2CK8HSO23X6O6LDS1/image-asset.png General Blog - Vaccine Classes: A Survey https://www.deplatformdisease.com/blog/category/Footwear monthly 0.5 https://www.deplatformdisease.com/blog/category/Fashion monthly 0.5 https://www.deplatformdisease.com/blog/category/Featured monthly 0.5 https://www.deplatformdisease.com/blog/tag/Patient+Experience monthly 0.5 https://www.deplatformdisease.com/blog/tag/Vaccine+Ingredients monthly 0.5 https://www.deplatformdisease.com/blog/tag/Aluminum monthly 0.5 https://www.deplatformdisease.com/blog/tag/vaccines monthly 0.5 https://www.deplatformdisease.com/blog/tag/research+design monthly 0.5 https://www.deplatformdisease.com/blog/tag/Myths monthly 0.5 https://www.deplatformdisease.com/blog/tag/Pandemic monthly 0.5 https://www.deplatformdisease.com/blog/tag/mRNA monthly 0.5 https://www.deplatformdisease.com/blog/tag/Vaccines monthly 0.5 https://www.deplatformdisease.com/blog/tag/T+cells monthly 0.5 https://www.deplatformdisease.com/blog/tag/ethics monthly 0.5 https://www.deplatformdisease.com/blog/tag/Epidemiology monthly 0.5 https://www.deplatformdisease.com/blog/tag/Formaldehyde monthly 0.5 https://www.deplatformdisease.com/blog/tag/Flu monthly 0.5 https://www.deplatformdisease.com/blog/tag/COVID-19 monthly 0.5 https://www.deplatformdisease.com/blog/tag/epidemiology monthly 0.5 https://www.deplatformdisease.com/blog/tag/SARS-CoV-2 monthly 0.5 https://www.deplatformdisease.com/blog/tag/Immunology monthly 0.5 https://www.deplatformdisease.com/blog/tag/immunology monthly 0.5 https://www.deplatformdisease.com/blog/tag/Blaylock monthly 0.5 https://www.deplatformdisease.com/blog/tag/Th1%2FTh2 monthly 0.5 https://www.deplatformdisease.com/blog/tag/Long-term+Effects monthly 0.5 https://www.deplatformdisease.com/blog/tag/AIDS monthly 0.5 https://www.deplatformdisease.com/blog/tag/Adjuvants monthly 0.5 https://www.deplatformdisease.com/blog/tag/Pharmacology monthly 0.5 https://www.deplatformdisease.com/blog/tag/Vaccine+Efficacy monthly 0.5 https://www.deplatformdisease.com/blog/tag/Virology monthly 0.5 https://www.deplatformdisease.com/blog/tag/herd+immunity monthly 0.5 https://www.deplatformdisease.com/blog/tag/Vaccinology monthly 0.5 https://www.deplatformdisease.com/blog/tag/Hydroxychloroquine monthly 0.5 https://www.deplatformdisease.com/blog/tag/RSV monthly 0.5 https://www.deplatformdisease.com/blog/tag/HIV monthly 0.5 https://www.deplatformdisease.com/blog/tag/infectious+disease monthly 0.5 https://www.deplatformdisease.com/blog/tag/Influenza monthly 0.5 https://www.deplatformdisease.com/blog/tag/HCQ monthly 0.5 https://www.deplatformdisease.com/blog/tag/Vaccine+Effectiveness monthly 0.5 https://www.deplatformdisease.com/blog/tag/Herd+Immunity monthly 0.5 https://www.deplatformdisease.com/blog/tag/Mythbusting monthly 0.5 https://www.deplatformdisease.com/special-topics daily 0.75 2023-06-11 https://www.deplatformdisease.com/special-topics/vitamin-k monthly 0.5 2023-06-11 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604875719806-II8GLVUPZBCZYS8JNWW8/image-asset.png Special Topics - Vitamin K at Birth: Everything You Ever Wanted To Know From Robbins, S., Cotran, R., Kumar, V., Abbas, A. and Aster, J., 2020. Pathologic Basis Of Disease. 10th ed. Philadelphia, PA: Saunders Elsevier. Figure 4.4 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1605493627067-RKQNGHRKWXPLW2AXRL7Y/Screen+Shot+2020-11-15+at+9.27.03+PM.png Special Topics - Vitamin K at Birth: Everything You Ever Wanted To Know Lichtman, M. and Williams, W., 2017. Williams Hematology. 9th ed. New York: McGraw-Hill Medical. Figure 114-1 on the balance between coagulation and anticoagulation. Thrombin represents a link between both coagulation and anticoagulation. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1605483482208-FOL5X763E72LC5F7LD26/Screen+Shot+2020-11-15+at+6.37.04+PM.png Special Topics - Vitamin K at Birth: Everything You Ever Wanted To Know The literal warning from the vitamin K package insert that says it will not spontaneously induce clotting e.g. if someone is bleeding. Vitamin K is not a styptic. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1605050593773-4K4XFYS571OK59A2TH6H/Screen+Shot+2020-11-10+at+6.23.10+PM.png Special Topics - Vitamin K at Birth: Everything You Ever Wanted To Know Newman, P. and Shearer, M., 2008. Metabolism and cell biology of vitamin K. Thrombosis and Haemostasis, 100(10), pp.530-547. Figure 2; Presents an overview of the transport of vitamin K throughout the body. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1605478883297-XZCTAJNB2RXL9JJSNAS5/image-asset.png Special Topics - Vitamin K at Birth: Everything You Ever Wanted To Know From Boron, W. and Boulpaep, E., 2017. Medical Physiology. 3rd ed. Elsevier. Figure 18-12 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1605494582301-QA5K8O74NPZ9HUXVELII/Screen+Shot+2020-11-15+at+9.42.59+PM.png Special Topics - Vitamin K at Birth: Everything You Ever Wanted To Know From Boron, W. and Boulpaep, E., 2017. Medical Physiology. 3rd ed. Elsevier. Figure 18-12 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1605228164764-DL328P5J9RBZ5WRRZRI7/Screen+Shot+2020-11-12+at+7.42.40+PM.png Special Topics - Vitamin K at Birth: Everything You Ever Wanted To Know https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1605228116261-9H836IX6RVSO1V4B9IE8/Screen+Shot+2020-11-12+at+7.41.53+PM.png Special Topics - Vitamin K at Birth: Everything You Ever Wanted To Know https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1605219122459-DWQZORNN5F721D6QR06I/Screen+Shot+2020-11-12+at+5.11.58+PM.png Special Topics - Vitamin K at Birth: Everything You Ever Wanted To Know Table 2 from Shearer, M. J. (2009). Vitamin K deficiency bleeding (VKDB) in early infancy. Blood Reviews, 23(2), 49–59. doi:10.1016/j.blre.2008.06.001 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1605487163349-8YV25D1625CYT6EE3RWU/Screen+Shot+2020-11-15+at+7.37.29+PM.png Special Topics - Vitamin K at Birth: Everything You Ever Wanted To Know SOEDIRMAN J, DE BRUIJN E, MAES R, HANCK A, GRÜTER J. Pharmacokinetics and tolerance of intravenous and intramuscular phylloquinone(vitamin K1) mixed micelles formulation. British Journal of Clinical Pharmacology. 1996;41(6):517-523. Figure 2 a-f https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1605493904677-QLAUCENTT5JKZ1HY5J99/Screen+Shot+2020-11-15+at+9.31.26+PM.png Special Topics - Vitamin K at Birth: Everything You Ever Wanted To Know Wiener, C., Brown, C., Houston, B., Fauci, A., Kasper, D., Hauser, S., Longo, D., Jameson, J. and Loscalzo, J., 2020. Harrison's Principles Of Internal Medicine. 20th ed. Figure 61-3 which demonstrates the functional form of activated protein C. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1605233958281-AC8044MZ67COPSFDBPSA/Screen+Shot+2020-11-12+at+9.19.15+PM.png Special Topics - Vitamin K at Birth: Everything You Ever Wanted To Know From Hoffman, R., Benz, E., Silberstein, L., Heslop, H., Weitz, J., Anastasi, J., Salama, M. and Abutalib, S., 2017. Hematology Basic Principles And Practice. 7th ed. Philadelphia, PA: Elsevier Figure 126.2 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1605490590170-WK3IVDFHK0C1KDQKG931/Screen+Shot+2020-11-15+at+8.36.25+PM.png Special Topics - Vitamin K at Birth: Everything You Ever Wanted To Know Per H, Arslan D, Gumus H, Coşkun A, Kumandas S. Intracranial Hemorrhages and Late Hemorrhagic Disease Associated Cholestatic Liver Disease. Pediatric Research. 2010;68:396-396. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1605493680061-EFCWI2ZXB8GGG91ZZ8YB/Screen+Shot+2020-11-15+at+9.27.53+PM.png Special Topics - Vitamin K at Birth: Everything You Ever Wanted To Know Hoffman, R., Benz, E., Silberstein, L., Heslop, H., Weitz, J., Anastasi, J., Salama, M. and Abutalib, S., 2017. Hematology Basic Principles And Practice. 7th ed. Philadelphia, PA: Elsevier. Figure 126.4 which demonstrates the Protein Case (pronounced “C”-”ase”) complex composed of thrombomodulin, protein C, and factor IIa (thrombin) which produces activated protein C, the major effector protein of anticoagulation which also depends on vitamin K. https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604870730996-X69AL742BP6NCNAGUKL4/Screen+Shot+2020-11-08+at+4.25.24+PM.png Special Topics - Vitamin K at Birth: Everything You Ever Wanted To Know Martin, R., Fanaroff, A. and Walsh, M., 2017. Fanaroff And Martin's Neonatal-Perinatal Medicine. 5th ed. Elsevier. Figure 33-1 https://www.deplatformdisease.com/special-topics/tag/Newborns monthly 0.5 https://www.deplatformdisease.com/special-topics/tag/Vitamin+K+Deficiency+Bleeding monthly 0.5 https://www.deplatformdisease.com/special-topics/tag/VKDB monthly 0.5 https://www.deplatformdisease.com/special-topics/tag/Vitamin+K monthly 0.5 https://www.deplatformdisease.com/vpd daily 0.75 2021-03-14 https://www.deplatformdisease.com/about daily 0.75 2020-12-07 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604197793648-7VYEGI9PPHCTK62L7S8Y/Screen%2BShot%2B2020-10-31%2Bat%2B10.29.11%2BPM.jpg About The US Childhood Vaccination Schedule https://www.deplatformdisease.com/contact daily 0.75 2021-01-03 https://images.squarespace-cdn.com/content/v1/5f9e108ff209714788ba4860/1604198084317-JBOCE4NKL6I57XJ6CCVN/Screen+Shot+2020-10-31+at+10.34.36+PM.png Contact That’s me. https://www.deplatformdisease.com/other-excellent-resources daily 0.75 2022-02-18