B.1.1.7: How many doses of the COVID-19 vaccine are needed? — Deplatform Disease

  • One dose is less reactogenic than two (the second dose tends to be worse in this regard).
  • You don’t have to worry about patient compliance- they don’t need to return for a second dose in 3–4 weeks depending on their vaccine.
  • Even if a single dose is less effective than a two-dose series, you may end up winning in terms of public health because you can immunize twice as many people. A less effective vaccine given to more people can be much more useful for public health than an extremely effective vaccine given to fewer people. This will depend on the specific efficacy of a single dose series.
  1. We don’t know very much at all about the protection of these vaccines from a single dose. The data from the clinical trials available to us are very limited as there are so few events and almost all participants received a second dose. I think one of the worst things that could happen would be to learn that the response from the first dose is not sufficiently anamnestic to produce a boosting effect with the second dose of vaccine given months later, and the second dose will function just like the first prime with a third dose needed at least 3 weeks later as a boost to yield robust immunity. It’s important to acknowledge mitigating factors here. In general, for virus-like particles and live attenuated vaccines, even a single dose of vaccine does produce anamnestic responses. In terms of the immune response they produce, they are very similar to live attenuated vaccines, and thus I am inclined to think that the concern about a total loss of immunological memory in the months following a single dose is not likely. Mouse studies examining a single dose of SARS-CoV-2 mRNA vaccines do suggest long-lived anamnestic responses which is excellent. Nonetheless, it would be great to have the data.
  2. The data above from Pfizer/BioNTech and Moderna’s vaccines show low titers before the boosting dose in the elderly (look at day 21 for Pfizer and day 29 for Moderna). I don’t like the idea of giving them a single dose, and making them wait months to receive the second, except perhaps in the case that they have already had COVID-19 before receiving the first dose.
  3. At this point I don’t have any significant concerns about antibody-dependent enhancement in COVID-19 (although I guess I better not count my emerging variants before they hatch). Nonetheless, a single dose series will not perform as well as a prime-boost regimen as planned, and we know the titers would be lower. Subneutralizing titers in other diseases are shown directly to be the cause of antibody-dependent enhancement. Hence there is a very remote but distinct possibility that giving people just one dose will open them up to additional harm.
  4. Perhaps the strongest argument comes from @notdred:

References

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  2. Florko N, Goldhill O, Branswell H, Boodman E, Cooney E. 2020 Dec 29. Frustration over vaccine rollout grows as new variant reported in U.S. Statnews.com. [accessed 2021 Jan 2]. https://www.statnews.com/2020/12/29/public-health-experts-grow-frustrated-with-pace-of-covid-19-vaccine-rollout/.
  3. Flower TG, Buffalo CZ, Hooy RM, Allaire M, Ren X, Hurley JH. 2020. Structure of SARS-CoV-2 ORF8, a rapidly evolving coronavirus protein implicated in immune evasion. bioRxivorg. doi:10.1101/2020.08.27.270637. http://dx.doi.org/10.1101/2020.08.27.270637.
  4. Lederer K, Castaño D, Gómez Atria D, Oguin TH 3rd, Wang S, Manzoni TB, Muramatsu H, Hogan MJ, Amanat F, Cherubin P, et al. 2020. SARS-CoV-2 mRNA vaccines foster potent antigen-specific germinal center responses associated with neutralizing antibody generation. Immunity. 53(6):1281–1295.e5.
  5. Levin AT, Hanage WP, Owusu-Boaitey N, Cochran KB, Walsh SP, Meyerowitz-Katz G. 2020. Assessing the age specificity of infection fatality rates for COVID-19: systematic review, meta-analysis, and public policy implications. Eur J Epidemiol. 35(12):1123–1138.
  6. Mahase E. 2020. Covid-19: What have we learnt about the new variant in the UK? BMJ. 371:m4944.
  7. Plotkin SA, Orenstein W, Offit PA, Edwards KM. 2017. Plotkin’s Vaccines. 7th ed. Elsevier.
  8. Preliminary genomic characterisation of an emergent SARS-CoV-2 lineage in the UK defined by a novel set of spike mutations. 2020 Dec 18. Virological.org. [accessed 2021 Jan 2]. https://virological.org/t/preliminary-genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-the-uk-defined-by-a-novel-set-of-spike-mutations/563.
  9. Public Health England. Investigation of novel SARS-COV-2 variant Variant of Concern 202012/01. Gov.uk. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/947048/Technical_Briefing_VOC_SH_NJL2_SH2.pdf.
  10. Rich. 2018. Clinical immunology: Principles and practice. 5th ed. London, England: Elsevier Health Sciences.
  11. Tufekci Z, Mina M. 2020 Dec 18. Can We Do Twice as Many Vaccinations as We Thought? NY Times. [accessed 2021 Jan 2]. https://www.nytimes.com/2020/12/18/opinion/coronavirus-vaccine-doses.html.
  12. 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.
  13. Young BE, Fong S-W, Chan Y-H, Mak T-M, Ang LW, Anderson DE, Lee CY-P, Amrun SN, Lee B, Goh YS, et al. 2020. Effects of a major deletion in the SARS-CoV-2 genome on the severity of infection and the inflammatory response: an observational cohort study. Lancet. 396(10251):603–611.
  14. Zhang Y, Zhang J, Chen Y, Luo B, Yuan Y, Huang F, Yang T, Yu F, Liu J, Liu B, et al. 2020. The ORF8 protein of SARS-CoV-2 mediates immune evasion through potently downregulating MHC-I. bioRxiv. doi:10.1101/2020.05.24.111823. https://www.biorxiv.org/content/10.1101/2020.05.24.111823v1.full.pdf.
  15. Zinzula L. 2020. Lost in deletion: The enigmatic ORF8 protein of SARS-CoV-2. Biochem Biophys Res Commun. doi:10.1016/j.bbrc.2020.10.045. [accessed 2021 Jan 2]. http://dx.doi.org/10.1016/j.bbrc.2020.10.045.

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Edward Nirenberg

Edward Nirenberg

I write about vaccines here. You can find me on Twitter @enirenberg and at deplatformdisease.com (where I publish the same content without a paywall)