Partial immunity and SARS-CoV-2 mutations-Response.

Hanage and Russell conjecture [see also ([ 1 ][1])] that intermediate levels of immunity may sufficiently restrict within-host viral population size and thus limit adaptive mutations. The evolutionary model in our Research Article encompasses a wide range of scenarios, including the optimistic one Hanage and Russell propose (see scenario 1 in Fig. 4A of the Research Article). However, we also argued that uncertainties in immunodynamics, and in particular evolutionary dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), dominate our ability to project key scenarios. We therefore produced generic models in an effort to encompass this variability while providing a useful framework for considering possible future outcomes. We would also like to clarify that the calculations for evolutionary potential in our Research Article involve only infections after natural or vaccinal immunity has waned [i.e., I S (secondary infection after waned natural immunity), I S1 (infection after waned one-dose vaccinal immunity), and I S2 (infection after waned two-dose vaccinal immunity), see Fig. 1]. Our accompanying interactive online application allows for the exploration of the effect of an even wider range of parameters on immunological and epidemiological outcomes. We stress that the understanding of viral phylodynamics (the intersection of the epidemiological and evolutionary dynamics of pathogens) is still in its infancy, especially for novel pathogens like SARS-CoV-2. We therefore believe that exploring the resulting uncertainty is key. Understanding the dynamics of different classes of individuals experiencing infections after the waning of natural or vaccinal immunity will be crucial for teasing out drivers of viral immune escape (i.e., the ability of a virus to evolve to evade host immune factors); this is at the heart of our model. Along these lines, and as we highlight in the Research Article, an important area of future work will be to develop phylodynamic models with explicit within-host dynamics ([ 2 ][2]). The other major source of uncertainties is in epidemiological outcomes. In their Letter, Hanage and Russell emphasize the likely epidemiological importance of widespread vaccine deployment. This echoes a conclusion of our Research Article, wherein we stress that short-term dose sparing deployment of a vaccine reduces infections and buys much time in public health planning. However, we also stressed the range of uncertainties that may modulate the longer-term outcomes of this strategy; in particular, less robust immunity could lead to more complex epidemiological and evolutionary outcomes. 1. [↵][3]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); . 2. [↵][4]1. D. H. Morris et al ., eLife 9, e62105 (2020). [OpenUrl][5][CrossRef][6][PubMed][7] [1]: #ref-1 [2]: #ref-2 [3]: #xref-ref-1-1 "View reference 1 in text" [4]: #xref-ref-2-1 "View reference 2 in text" [5]: {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 [6]: /lookup/external-ref?access_num=10.7554/eLife.62105&link_type=DOI [7]: /lookup/external-ref?access_num=33174838&link_type=MED&atom=%2Fsci%2F372%2F6540%2F354.2.atom