Abstract:

  When vaccines are in limited supply, expanding the number of people who receive some vaccine can reduce disease and mortality compared to concentrating vaccines in a subset of the population. A corollary of such dose-sparing strategies is that vaccinated individuals may have less protective immunity. Concerns have been raised that expanding the fraction of the population with partial immunity to SARS-CoV-2 could increase selection for vaccine escape variants, ultimately undermining vaccine effectiveness. We argue that although this is possible, preliminary evidence instead suggests such strategies should slow the rate of vaccine or immune escape. As long as vaccination provides some protection against escape variants, the corresponding reduction in prevalence and incidence should reduce the rate at which new variants are generated and the speed of adaptation. Because there is little evidence for efficient immune selection of SARS-CoV-2 during typical infections, these population-level effects are likely to dominate vaccine-induced evolution.

Conclusion:

  We propose that dose-sparing strategies, which could have large public health benefits, not be dismissed out of concern that they might promote immune escape in SARS-CoV-2. In fact, multiple lines of evidence suggest that expanded vaccination coverage could reduce the rate of immune escape, providing an additional benefit of dose sparing beyond its immediate impact on disease. These beneficial effects hinge on the assumption that vaccination provides some protection against variants of SARS-CoV-2, or in other words, that vaccine effectiveness against the variants is not zero under dose sparing. Another requirement is that other fitness-enhancing mutations not be exclusively linked to vaccine escape mutations. Both of these assumptions appear currently met. We encourage research to refine understanding of vaccine effectiveness, immune pressure, and the evolutionary dynamics of SARS-CoV-2, and to investigate this problem more thoroughly.

Author Affiliation

  Department of Ecology and Evolution, University of Chicago, Chicago, IL, USA
  Department of Computer Science, University of Colorado Boulder, Boulder, CO, USA
  BioFrontiers Institute, University of Colorado Boulder, Boulder, CO, USA
  Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, MA, USA
  Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA