Testing fractional doses of COVID-19 vaccines

Proc Natl Acad Sci U S A. 2022 Feb 22;119(8):e2116932119. doi: 10.1073/pnas.2116932119.


Due to the enormous economic, health, and social costs of the COVID-19 pandemic, there are high expected social returns to investing in parallel in multiple approaches to accelerating vaccination. We argue there are high expected social returns to investigating the scope for lowering the dosage of some COVID-19 vaccines. While existing evidence is not dispositive, available clinical data on the immunogenicity of lower doses combined with evidence of a high correlation between neutralizing antibody response and vaccine efficacy suggests that half or even quarter doses of some vaccines could generate high levels of protection, particularly against severe disease and death, while potentially expanding supply by 450 million to 1.55 billion doses per month, based on supply projections for 2021. An epidemiological model suggests that, even if fractional doses are less effective than standard doses, vaccinating more people faster could substantially reduce total infections and deaths. The costs of further testing alternative doses are much lower than the expected public health and economic benefits. However, commercial incentives to generate evidence on fractional dosing are weak, suggesting that testing may not occur without public investment. Governments could support either experimental or observational evaluations of fractional dosing, for either primary or booster shots. Discussions with researchers and government officials in multiple countries where vaccines are scarce suggests strong interest in these approaches.

Keywords: COVID-19; dose stretching; fractional dosing; pandemic; vaccines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19 / immunology
  • COVID-19 / mortality
  • COVID-19 / prevention & control*
  • COVID-19 / virology
  • COVID-19 Vaccines / administration & dosage
  • COVID-19 Vaccines / economics
  • COVID-19 Vaccines / supply & distribution*
  • Developed Countries
  • Developing Countries
  • Drug Administration Schedule
  • Humans
  • Immunization, Secondary / economics
  • Immunization, Secondary / methods*
  • Models, Statistical*
  • Off-Label Use
  • SARS-CoV-2 / drug effects
  • SARS-CoV-2 / immunology
  • SARS-CoV-2 / pathogenicity
  • Survival Analysis
  • Vaccination / economics
  • Vaccination / methods*


  • COVID-19 Vaccines