ABSTRACT
Since the COVID-19 pandemic began in 2020, viral sequencing has documented 131 individual mutations in the viral spike protein across 48 named variants. To determine the ability of vaccine-mediated humoral immunity to keep pace with continued SARS-CoV-2 evolution, we assessed the neutralization potency of sera from 76 vaccine recipients collected after 2 to 6 immunizations against a comprehensive panel of mutations observed during the pandemic. Remarkably, while many individual mutations that emerged between 2020 and 2022 exhibit escape from sera following primary vaccination, few escape boosted sera. However, progressive loss of neutralization was observed across newer variants, irrespective of vaccine doses. Importantly, an updated XBB.1.5 booster significantly increased titers against newer variants but not JN.1. These findings demonstrate that seasonal boosters improve titers against contemporaneous strains, but novel variants continue to evade updated mRNA vaccines, demonstrating the need for novel approaches to adequately control SARS-CoV-2 transmission.
Subject(s)
COVID-19ABSTRACT
SUMMARY Recent surveillance has revealed the emergence of the SARS-CoV-2 Omicron variant (BA.1/B.1.1.529) harboring up to 36 mutations in spike protein, the target of vaccine-induced neutralizing antibodies. Given its potential to escape vaccine-induced humoral immunity, we measured neutralization potency of sera from 88 mRNA-1273, 111 BNT162b, and 40 Ad26.COV2.S vaccine recipients against wild type, Delta, and Omicron SARS-CoV-2 pseudoviruses. We included individuals that were vaccinated recently (<3 months), distantly (6-12 months), or recently boosted, and accounted for prior SARS-CoV-2 infection. Remarkably, neutralization of Omicron was undetectable in most vaccinated individuals. However, individuals boosted with mRNA vaccines exhibited potent neutralization of Omicron only 4-6-fold lower than wild type, suggesting that boosters enhance the cross-reactivity of neutralizing antibody responses. In addition, we find Omicron pseudovirus is more infectious than any other variant tested. Overall, this study highlights the importance of boosters to broaden neutralizing antibody responses against highly divergent SARS-CoV-2 variants.
Subject(s)
COVID-19ABSTRACT
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 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 negative neutralization titers. Bulk and cytotoxic T-cell responses were higher in mRNA1273 and BNT162b2 than Ad26.COV2.S recipients, and <50% of vaccinees demonstrate CD8+ T-cell responses to spike peptides. 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. 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.