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

Abstract

Background Understanding immunogenicity and effectiveness of SARS-CoV-2 vaccines is critical to guide rational use. Methods We compared the immunogenicity of mRNA-1273, BNT-162b2 or Ad26.COV2.S in healthy ambulatory adults in Massachusetts, USA. To correlate immunogenicity with effectiveness of the three vaccines, 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 three FDA EUA vaccines deployed in the USA.

Neutralization breadth of SARS-CoV-2 viral variants following primary series and booster SARS-CoV-2 vaccines in patients with cancer

“…Consistent with the overall CANVAX population and other studies ( Naranbhai et al., 2021b ; Tada et al., 2021 ), neutralization of wildtype SARS-CoV-2 was highest for mRNA1273 recipients, followed by BNT162b2, and lowest among patients receiving Ad26.COV2.S. Adjusting for covariates, neutralization was lower among BNT162b2 recipients than mRNA1273 for the alpha, gamma, and delta variants ( Figure 1 and Table S2 ).…”

“…First, to achieve the greatest neutralizing breadth, the most immunogenic vaccine may be preferred as the primary series for patients at high risk, where feasible. Second, the hierarchy of effectiveness of the 3 FDA EUA vaccines in preventing breakthrough infection by variants, where mRNA1273 provides the highest protection, followed by BNT162b2 and then Ad26.COV2.S ( Naranbhai et al., 2021b ) are likely accounted for by differences in immunogenicity against wildtype SARS-CoV-2. Finally, booster doses with wildtype vaccines would be expected to increase protection against variants in patients with cancer, even as we await the next generation of vaccines.…”

Humoral and Cellular Responses to COVID-19 Vaccines in SARS-CoV-2 Infection-Naïve and -Recovered Korean Individuals

“…In our study comprising 18 individuals, 61% of the single-dose vaccinees were administered ChAdOX1, and the others were administered mRNA vaccines: 22% BNT162b2 and 17% mRNA-1273. Similar to the conditions observed in response to Ad26.COV2.S [20], no significant immunological differences were observed between the ChAdOX1 and mRNA vaccines, regardless of the dose, in the recovered individuals (Figures S1 and 2). Ebinger et al reported that the anti-S RBD antibody titer and ACE2binding capacity after a single dose were similar to the response seen after two doses of the BNT162b2 vaccine in previously infected healthcare workers [9].…”

“…Therefore, protective immunity seems to be significantly strengthened by COVID-19 vaccination in SARS-CoV-2-recovered individuals. A single dose of BNT162b2, mRNA-1273, or Ad26.COV2.S induced higher anti-S antibody titers in the recovered individuals than in the unvaccinated convalescent individuals, regardless of the vaccine type [20]. In our study comprising 18 individuals, 61% of the single-dose vaccinees were administered ChAdOX1, and the others were administered mRNA vaccines: 22% BNT162b2 and 17% mRNA-1273.…”

Higher SARS-CoV-2 Spike Binding Antibody Levels and Neutralization Capacity 6 Months after Heterologous Vaccination with AZD1222 and BNT162b2

“…We were intrigued by our findings of comparable neutralization capacities against the Wuhan-Hu-1 and Delta peptides combined with very strong correlations between both, independent of whether antibodies resulted from a homologous or heterologous primeboost regimen. As we employed surrogate virus neutralization assays with RBD peptides only, our findings suggest that mutations besides the Delta-specific L452R and T478K are responsible for the loss of neutralization described in conventional virus neutralization tests [22,23]. Moreover, our findings attribute a reduced vaccine effectiveness against Delta not only to the loss of susceptibility against neutralizing antibodies but also to an altered T cell reactivity and/or increased viral transmission [11,24,25].…”