Comparative Immunogenicity and Effectiveness of mRNA-1273, BNT162b2, and Ad26.COV2.S COVID-19 Vaccines

J Infect Dis. 2022 Apr 1;225(7):1141-1150. doi: 10.1093/infdis/jiab593.

Abstract

Background: Understanding immunogenicity and effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines is critical to guide rational use.

Methods: We compared the immunogenicity of mRNA-1273, BNT-162b2, and Ad26.COV2.S in healthy ambulatory adults. We performed an inverse-variance meta-analysis of population-level effectiveness from public health reports in > 40 million individuals.

Results: A single dose of either mRNA vaccine yielded comparable antibody and neutralization titers to convalescent individuals. Ad26.COV2.S yielded lower antibody concentrations and frequently undetectable neutralization titers. Bulk and cytotoxic T-cell responses were higher in mRNA1273 and BNT162b2 than Ad26.COV2.S recipients. Regardless of vaccine, <50% of vaccinees demonstrated CD8+ T-cell responses. Antibody concentrations and neutralization titers increased comparably after the first dose of either vaccine, and further in recipients of a second dose. Prior infection was associated with high antibody concentrations and neutralization even after a single dose and regardless of vaccine. Neutralization of Beta, Gamma, and Delta strains were poorer regardless of vaccine. In meta-analysis, relative to mRNA1273 the effectiveness of BNT162b2 was lower against infection and hospitalization, and Ad26COV2.S was lower against infection, hospitalization, and death.

Conclusions: Variation in the immunogenicity correlates with variable effectiveness of the 3 vaccines deployed in the United States.

Keywords: Ad26.COV2.S; BNT162b2; SARS CoV-2; T cells; death; effectiveness; hospitalization; immunogenicity; mRNA-1273; neutralization.

Publication types

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

MeSH terms

  • 2019-nCoV Vaccine mRNA-1273
  • Ad26COVS1*
  • Adult
  • BNT162 Vaccine
  • COVID-19 Vaccines
  • COVID-19* / prevention & control
  • Humans
  • Immunogenicity, Vaccine
  • SARS-CoV-2 / genetics
  • Vaccines, Synthetic
  • mRNA Vaccines

Substances

  • Ad26COVS1
  • COVID-19 Vaccines
  • Vaccines, Synthetic
  • mRNA Vaccine
  • mRNA Vaccines
  • 2019-nCoV Vaccine mRNA-1273
  • BNT162 Vaccine