Antibody Responses and Infection Prevention Following the Sixth Vaccination Using the BA.1 Bivalent COVID-19 Vaccine Among Healthcare Workers During the XBB Variant Dominance in Japan

The effect of the antibodies elicited by bivalent mRNA vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (the original strain and Omicron variant BA.1) on preventing coronavirus disease 2019 (COVID-19) onset during the XBB variant dominance remains unknown. We conducted a prospective cohort study at Chiba University Hospital and examined healthcare workers who received the Pfizer-BioNTech bivalent mRNA COVID-19 vaccine (targeting the original and Omicron BA.1) as their sixth dose of COVID-19 vaccine. The serum antibodies against SARS-CoV-2 spike (S) protein were measured quantitatively. Participants who were not infected during the 60-day observation period following the sixth vaccination had significantly higher S antibody titers than those who were newly infected (27,756 U/mL, 95% confidence interval [CI] 24,988-30,831 U/mL vs. 15,321 U/mL, 95% CI 10,824-21,688 U/mL; P < 0.05). S antibody titer ≥15,500 U/mL decreased the risk of infection by 84%. Neutralizing antibody titers against the XBB.1.16 and XBB.1.42 variants were higher in age- and sex-matched non-infected individuals than in newly infected individuals during the post-vaccination observation period. S antibody titers were highly correlated with neutralizing antibody titers. In conclusion, after the sixth vaccination with a bivalent mRNA COVID-19 vaccine, high S antibody titers correlated with disease prevention, even in the presence of the XBB variants.