Epidemiological and evolutionary considerations of SARS-CoV-2 vaccine dosing regimes

Science. 2021 Apr 23;372(6540):363-370. doi: 10.1126/science.abg8663. Epub 2021 Mar 9.


Given vaccine dose shortages and logistical challenges, various deployment strategies are being proposed to increase population immunity levels to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Two critical issues arise: How timing of delivery of the second dose will affect infection dynamics and how it will affect prospects for the evolution of viral immune escape via a buildup of partially immune individuals. Both hinge on the robustness of the immune response elicited by a single dose as compared with natural and two-dose immunity. Building on an existing immuno-epidemiological model, we find that in the short term, focusing on one dose generally decreases infections, but that longer-term outcomes depend on this relative immune robustness. We then explore three scenarios of selection and find that a one-dose policy may increase the potential for antigenic evolution under certain conditions of partial population immunity. We highlight the critical need to test viral loads and quantify immune responses after one vaccine dose and to ramp up vaccination efforts globally.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological
  • Adaptive Immunity
  • COVID-19 / epidemiology
  • COVID-19 / immunology
  • COVID-19 / prevention & control*
  • COVID-19 / virology
  • COVID-19 Vaccines / administration & dosage*
  • COVID-19 Vaccines / immunology*
  • Disease Susceptibility
  • Evolution, Molecular*
  • Humans
  • Immune Evasion
  • Immunization Schedule
  • Immunogenicity, Vaccine
  • Models, Theoretical
  • Mutation
  • SARS-CoV-2 / genetics*
  • SARS-CoV-2 / immunology*
  • Selection, Genetic
  • Vaccination


  • COVID-19 Vaccines