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

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. SARS-CoV-2 vaccines differ in immunogenicity (by multiple humoral and T-cell measures): mRNA1273 induced the strongest responses following by BNT162b2; Ad26.COV2.S induced weak responses. Differences in immunogenicity predict population-level effectiveness against infection, hospitalization, or death (mRNA1273 > bnt162b2 > Ad26.COV2.S).

Automated summary

Understanding the immunogenicity and effectiveness of SARS-CoV-2 vaccines is crucial. This study compared the immunogenicity and effectiveness of mRNA-1273, BNT-162b2, and Ad26.COV2.S in healthy adults. The results showed that mRNA vaccines and convalescent individuals had comparable antibody and neutralization titers, while Ad26.COV2.S had lower antibody concentrations. mRNA1273 and BNT162b2 induced higher T-cell responses. Prior infection was associated with high antibody concentrations and neutralization even after a single dose. Meta-analysis showed differences in effectiveness against infection, hospitalization, and death, with mRNA1273 being the most effective.