Discussion
SARS-CoV-2 infection
ADVERSE REACTIONS, SARS-COV-2 INFECTION
The rapid evolution of antigenically divergent SARS-CoV-2 variants precipitated development of booster immunizations to maintain protection against COVID-19 and regulatory agencies have authorized variant-containing bivalent booster vaccines globallyThe 50 µg bivalent vaccine mRNA-1273.222 elicited higher BA.4/BA.5 neutralizing antibody responses compared to the original 50 µg mRNA-1273 28 days after the booster dose, in participants with and without evidence of SARS-CoV-2 infection on the day of the booster dose. Additionally, mRNA-1273.222 exhibited cross-neutralization against divergent variants which are not contained in the vaccine, such as BQ.1.1, XBB.1 and XBB.1.5, although the antibody titers for these variants were lower compared to BA.4/BA.5. These results are consistent with cross-neutralization observed after the BA.1-Omicron-containing mRNA-1273.214 bivalent vaccine dose as titers against Omicron BA.4/BA.5, BQ.1.1 and XBB.1 were lower compared to the matched BA.1 variant in the mRNA-1273.214 vaccineOur interim results also indicate that the incidence of adverse reactions with the Omicron BA.4/BA.5-containing bivalent booster mRNA-1273.222 was similar to that of prior doses of mRNA-1273 (refs. Limitations include that the study was not randomized. Given that the Omicron BA.4/BA.5 vaccine update had already been recommended as the standard-of-careIn conclusion, given that SAS-CoV-2 variants are most likely to continue to emerge, our study provides a model for rapid clinical evaluation of a COVID-19 vaccine when a booster update and deployment is needed. Our results indicate that the Omicron BA.4/BA.5 bivalent mRNA-1273.222 vaccine increased neutralizing antibody responses against Omicron variants, with no new safety concerns compared to the original vaccine mRNA-1273. Continuous monitoring of cross-neutralization and vaccine effectiveness are needed to ensure updated vaccination strategies against COVID-19.