Evaluation of COVID-19 vaccination strategies with a delayed second dose

PLoS Biol. 2021 Apr 21;19(4):e3001211. doi: 10.1371/journal.pbio.3001211. eCollection 2021 Apr.

Abstract

Two of the Coronavirus Disease 2019 (COVID-19) vaccines currently approved in the United States require 2 doses, administered 3 to 4 weeks apart. Constraints in vaccine supply and distribution capacity, together with a deadly wave of COVID-19 from November 2020 to January 2021 and the emergence of highly contagious Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants, sparked a policy debate on whether to vaccinate more individuals with the first dose of available vaccines and delay the second dose or to continue with the recommended 2-dose series as tested in clinical trials. We developed an agent-based model of COVID-19 transmission to compare the impact of these 2 vaccination strategies, while varying the temporal waning of vaccine efficacy following the first dose and the level of preexisting immunity in the population. Our results show that for Moderna vaccines, a delay of at least 9 weeks could maximize vaccination program effectiveness and avert at least an additional 17.3 (95% credible interval [CrI]: 7.8-29.7) infections, 0.69 (95% CrI: 0.52-0.97) hospitalizations, and 0.34 (95% CrI: 0.25-0.44) deaths per 10,000 population compared to the recommended 4-week interval between the 2 doses. Pfizer-BioNTech vaccines also averted an additional 0.60 (95% CrI: 0.37-0.89) hospitalizations and 0.32 (95% CrI: 0.23-0.45) deaths per 10,000 population in a 9-week delayed second dose (DSD) strategy compared to the 3-week recommended schedule between doses. However, there was no clear advantage of delaying the second dose with Pfizer-BioNTech vaccines in reducing infections, unless the efficacy of the first dose did not wane over time. Our findings underscore the importance of quantifying the characteristics and durability of vaccine-induced protection after the first dose in order to determine the optimal time interval between the 2 doses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • COVID-19 / epidemiology
  • COVID-19 / immunology
  • COVID-19 / prevention & control*
  • COVID-19 Vaccines / administration & dosage*
  • COVID-19 Vaccines / supply & distribution
  • Hospitalization / statistics & numerical data
  • Humans
  • Immunization Schedule
  • Immunization, Secondary
  • Models, Statistical
  • Mortality
  • SARS-CoV-2 / immunology*
  • United States / epidemiology
  • Vaccination / methods*
  • Vaccination / statistics & numerical data

Substances

  • COVID-19 Vaccines