The fourth dose of mRNA COVID-19 vaccine following 12 different three-dose regimens: Safety and immunogenicity to Omicron BA.4/BA.5

Abstract

Objective:To investigate the reactogenicity and immunogenicity of the fourth dose using mRNA vaccines after different three-dose regimens and to compare the 30 μg BNT162b2 and 50 μg mRNA-1273 vaccines.Methods:This prospective cohort study was conducted between June and October 2022. The self-recorded reactogenicity was evaluated on the subsequent 7 days after a fourth dose. Binding and neutralizing activity of antibodies against the Omicron BA.4/5 variants were determined.Results:Overall, 292 healthy adults were enrolled and received BNT162b2 or mRNA-1273. Reactogenicity was mild to moderate and well-tolerated after a few days. Sixty-five individuals were excluded. Thus, 227 eligible individuals received a fourth booster dose of BNT162b2 (n=109) and mRNA-1273 (n=118). Most participants, regardless the type of previous three dose regimens, elicited a significantly high level of binding antibodies and neutralizing activity against the Omicron BA.4/5 28 days after a fourth dose. The neutralizing activity against the Omicron BA.4/5 between the BNT162b2 (82.8%) and mRNA-1273 (84.2%) groups was comparable with a median ratio of 1.02.Conclusion:This study found that the BNT162b2 and mRNA-1273 vaccines can be used as a fourth booster dose for individuals who were previously immunized with any prior mix and match three dose COVID-19 vaccine.