Public Comment by Rob Wallace, PhD, submitted to the FDA’s Vaccines and Related Biological Products Advisory Committee regarding the future vaccination regimens addressing COVID-19.
I’m an evolutionary epidemiologist. I mapped statistical phylogeographies, including molecular evolutionary traces, for HPAI H5N1 under CDC advisor Walter Fitch at UC Irvine 1-2. I have consulted for the CDC and am commenting here on behalf of the People’s CDC3.
An underlying supposition of the draft VRBPAC recommendations concerning changing the composition and schedule of COVID-19 vaccination is a putative analogy between SARS-CoV-2 and influenza. Metaphors are necessary, but often problematic. Comparing two problems does not make them the same, a distinction well-explored in science4 . The FDA Briefing Document on the topic pings back and forth between acknowledging the fallacy and indulging it.
I will speak on a technical issue here, but will note in passing the present administration’s efforts to end the pandemic by fiat than by deed, from the May 2021 recommendation that the vaccinated needn’t mask to the Impact Research memo5. These documented efforts place the present matter in a broader political economy. In framing its response to COVID-19 on the influenza model, the advisory committee risks turning the cause, the virus, into something we wish it was: just like influenza.
Influenza vaccination–as half-ass as it is–works in part because we can predict which strains will seed the next year’s pandemic6. Fitch and colleagues showed those H3 strains most evolved at 18 codons almost always served as the progenitor of the next year’s pandemic7-9.
There’s been some work in this direction on SARS-2, but even under optimistic modeling, the present population parameters do not place us near the kind of endemicity associated with seasonal influenza10-12. Punctuated equilibria on a schedule of the virus’s own making, not that of industrial production or any other broader objective, are the evolutionary order of the day. And we do not have a handle on that schedule, save perhaps, as recent work showed, SARS-2 variants are spreading faster than before upon emergence and the speed of the arrival of various Omicron subvariants was not deterred by the level of population vaccination13.
The implications are twofold. Constraining vaccination to once a year would only further handcuff a public health response already limited by an abandonment of nonpharmaceutical interventions. At the clinical level, vaccination alone offers better protection but no guarantee against reinfection and Long COVID14,15. At the evolutionary level, models by Okamoto et al. show losing NPI likely selects for changes in SARS-2’s reproductive strategy and the emergence of vaccine-resistant strains16,17.
In short, prevention, keeping people from getting infected in the first place, remains a critical contribution to preserving vaccine effectiveness. In the other direction, reducing the degrees of freedom we have in the types and scheduling of vaccine production only compounds the public health damage dropping NPI campaigns such as mask mandates and contact tracing produces18.
Secondly, the rationale here behind simplifying the vaccine schedule is all wrong. It isn’t the present scheduling that keeps booster coverage at a little over 16% of eligible Americans19. It’s the insistence in declaring a still rapidly evolving pandemic over and ending all those programs that would have helped vaccination programs succeed. The success of federal pharmaceutical campaigns depends on the NPI campaigns going door-to-door that two administrations running dropped. Do not operationalize an intervention that’s based on blaming unvaccinated Americans for that fiasco.
-  Wallace RG, HM HoDac, R Lathrop, and WM Fitch (2007) A statistical phylogeography of influenza A H5N1. Proceedings of the National Academy of Sciences, 104:4473-4478.
-  Wallace RG and WM Fitch (2008) Influenza A H5N1 immigration is filtered out at some international borders. PLoS ONE, 3(2): e1697.
-  Yee G (2011) Esteemed Professor Passes Away. New University, 5 April. https://newuniversity.org/2011/04/05/esteemed-professor-passes-away/.
-  https://peoplescdc.org/
-  Taylor C and BM Dewsbury (2018) On the problem and promise of metaphor use in science and science communication. J Microbiol Biol Educ. 19(1):19.1.46.
-  Kapur S (2022) Democrats turn against mask mandates as Covid landscape and voter attitudes shift. NBC News, 1 March. https://www.nbcnews.com/politics/politics-news/democrats-turn-mask-mandates covid-landscape-voter-attitudes-shift-rcna18043
-  Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases (NCIRD) (2022) Past Seasons’ Vaccine Effectiveness Estimates. 22 December. https://www.cdc.gov/flu/vaccines-work/past-seasons-estimates.html.
-  Fitch WM, RM Bush, CA Bender, and NJ Cox (1997) Long term trends in the evolution of H(3) HA1 human influenza type A. PNAS, 94(15):7712-7718
-  Bush RM, CA Bender, K Subbarao, NJ Cox, and WM Fitch (1999) Predicting the evolution of human Influenza A. Science, 286(5446):1921-1925.
-  Bush RM, WM Fitch, CA Bender, and NJ Cox (1999) Positive selection on the H3 hemagglutinin gene of human influenza virus A. Mol Biol Evol. 16(11):1457-65.
-  Maher MC, et al. (2022) Predicting the mutational drivers of future SARS-CoV-2 variants of concern. Science Translational Medicine, 14(633):eabk3445.
-  Mullin S, BV Wyk, JL Asher, SR Compton, HG Allore, and CJ Zeiss (2022) Modeling pandemic to endemic patterns of SARS-CoV-2 transmission using parameters estimated from animal model data. PNAS Nexus, 1(3):pgac096.
-  Cohen LE, DJ Spiro, and C Viboud C (2022) Projecting the SARS-CoV-2 transition from pandemicity to endemicity: Epidemiological and immunological considerations. PLoS Pathog, 18(6):e1010591
-  Beesley LJ, et al. (2022) SARS-CoV-2 variant transition dynamics are associated with vaccination rates, number of co-circulating variants, and natural immunity. bioRxiv, 21 November. https://www.biorxiv.org/content/10.1101/2022.11.18.517139v1.full
-  Nielsen KF, IR Moustsen-Helms, AB Schelde, MA Gram, H-D Emborg, et al. (2022) Vaccine effectiveness against SARS-CoV-2 reinfection during periods of Alpha, Delta, or Omicron dominance: A Danish nationwide study. PLoS Med 19(11): e1004037.
-  Davis HE, L McCorkell, JM Vogel, and EJ Topol (2023) Long COVID: major findings, mechanisms and recommendations. Nature Reviews Microbiology. https://doi.org/10.1038/s41579-022-00846-2
-  Okamoto KW, V Ong, RG Wallace, R Wallace, and LF Chaves (2023) When might host heterogeneity drive the evolution of asymptomatic, pandemic coronaviruses? Nonlinear Dyn. 111(1):927-949.
-  Okamoto K, L Chaves, R Wallace, and RG Wallace (2022) Governance is key to controlling SARS-CoV-2’s vaccine resistance. MedRxiv preprint. https://www.medrxiv.org/content/10.1101/2022.05.26.22275649v1.
-  Leech G, et al. (2022) Mask wearing in community settings reduces SARS-CoV-2 transmission. PNAS, 119(23):e2119266119.
-  Centers for Disease Control and Prevention (2023) Updated (Bivalent) Booster Dose. COVID Data Tracker. US Department of Health and Human Services, CDC, Atlanta, GA. 25 January. https://covid.cdc.gov/covid-data-tracker/#vaccinations_vacc-people-booster-percent-pop5