Partial immunity and SARS-CoV-2 mutations.

Abstract

In their Research Article, “Epidemiological and evolutionary considerations of SARS-CoV-2 vaccine dosing regimes” (this issue, p. [363][1]; published online 9 March), C. M. Saad-Roy et al. write that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine dosing regimens generating intermediate levels of immunity could accelerate the emergence of new variants that are capable of wholly or partially escaping immunity induced by prior infection or vaccination—immune-escape variants. Their argument assumes that such variants are most likely to arise through de novo mutation and selection in partially immune hosts (i.e., those people who have not mounted a strong immune response to infection or vaccination). However, for a pathogen like SARS-CoV-2 that typically transmits in the early stage of infection after relatively few cycles of replication ([ 1 ][2]), there is little opportunity for adaptive mutants to be generated and rise to a frequency that makes onward transmission likely. Simultaneously, there is good reason to think that intermediate levels of immunity should both reduce the probability of infection and limit the supply of adaptive mutations by restricting the viral population size within each vaccinated host ([ 2 ][3], [ 3 ][4]). Furthermore, viral loads appear lower in infections 12 to 28 days after a single dose of vaccine than in unvaccinated individuals, which likely translates to decreased transmission by vaccinated individuals ([ 4 ][5]). Because of limited opportunities for both mutation and selection within a host, the presence of immune-escape variants may be more important at the point of infection of immune individuals ([ 2 ][3], [ 3 ][4]). If so, what matters is the standing diversity of such variants in the population as a whole. Reducing numbers of infections through vaccination should then reduce opportunities for such diversity to be generated, transmitted, and selected. In short, vaccination is likely to make evolution slower, and this benefit may be realized by initially optimizing breadth of vaccine coverage, rather than strength of immunity. We do not advocate for delayed dosing strategies without further clinical evidence, and it is important to consider the issues raised by Saad-Roy et al. , which will depend on the properties of the vaccines involved. However, anxiety about the potential of vaccination to increase the emergence rate of immune-escape variants should be tempered by the low probability of the confluence of mutation, selection, and transmission as well as the enormous public health benefits of widespread vaccination. 1. [↵][6]1. X. He et al ., Nat. Med. 26, 672 (2020). [OpenUrl][7][CrossRef][8][PubMed][9] 2. [↵][10]1. D. H. Morris et al ., eLife 9, e62105 (2020). [OpenUrl][11][CrossRef][12][PubMed][13] 3. [↵][14]1. S. Cobey, 2. D. B. Larremore, 3. Y. H. Grad, 4. M. Lipsitch , “Concerns about SARS-CoV-2 evolution should not hold back efforts to expand vaccination,” preprint, Harvard University (2021); . 4. [↵][15]1. M. Levine-Tiefenbrun et al ., medrxiv 10.1101/2021.02.06.21251283v1 (2021). W.P.H. was paid to provide expert witness testimony in a litigation matter related in part to the expected duration of the COVID-19 pandemic. [1]: http://www.sciencemag.org/content/372/6540/363 [2]: #ref-1 [3]: #ref-2 [4]: #ref-3 [5]: #ref-4 [6]: #xref-ref-1-1 View reference 1 in text [7]: {openurl}?query=rft.jtitle%253DNat.%2BMed.%26rft.volume%253D26%26rft.spage%253D672%26rft_id%253Dinfo%253Adoi%252F10.7326%252FM20-3012%26rft_id%253Dinfo%253Apmid%252Fhttp%253A%252F%252Fwww.n%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [8]: /lookup/external-ref?access_num=10.7326/M20-3012&link_type=DOI [9]: /lookup/external-ref?access_num=http://www.n&link_type=MED&atom=%2Fsci%2F372%2F6540%2F354.1.atom [10]: #xref-ref-2-1 View reference 2 in text [11]: {openurl}?query=rft.jtitle%253DeLife%26rft.volume%253D9%26rft.spage%253De62105%26rft_id%253Dinfo%253Adoi%252F10.7554%252FeLife.62105%26rft_id%253Dinfo%253Apmid%252F33174838%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [12]: /lookup/external-ref?access_num=10.7554/eLife.62105&link_type=DOI [13]: /lookup/external-ref?access_num=33174838&link_type=MED&atom=%2Fsci%2F372%2F6540%2F354.1.atom [14]: #xref-ref-3-1 View reference 3 in text [15]: #xref-ref-4-1 View reference 4 in text