Neutralizing antibodies following three doses of BNT162b2 vaccine, breakthrough infection, and symptoms during the Omicron predominant wave

ABSTRACT

BackgroundData on the role of immunogenicity following the third vaccine dose against Omicron infection and coronavirus disease 2019 (COVID-19)-compatible symptoms of infection are limited. MethodsFirst we examined vaccine effectiveness (VE) of the third-dose against the second dose during the Omicron wave among the staff at a tertiary hospital in Tokyo. In a case-control study of a cohort of third vaccine recipients, we compared the pre-infection levels of live-virus neutralizing antibodies (NAb) against Omicron between breakthrough cases and their controls, who had close contact with COVID-19 patients. Among these cases, we examined the association between pre-infection NAb levels and the number of COVID-19-compatible symptoms experienced during the Omicron wave. ResultsAmong the 1456 participants for VE analysis, 60 (4%) breakthrough infections occurred during the Omicron wave (January to March 2022). The third-dose VE for infection, relative to the second dose was 54.6% (95% CI 14.0-76.0). Among the recipients of the third vaccine, pre-infection NAb levels against Omicron did not significantly differ between the cases and controls. Among the cases, those who experienced COVID-19-compatible symptoms had lower pre-infection NAb levels against Omicron than those who did not. ConclusionsThe third vaccine dose was effective in decreasing the risk of severe acute respiratory syndrome coronavirus 2 infection during the Omicron wave compared with the second dose. Among third-dose recipients, higher pre-infection NAb levels may not be associated with a lower risk of Omicron infection. Contrarily, they may be associated with fewer symptoms of infection. SummaryThe third vaccine dose reduced SARS-CoV-2 infection risk during the Omicron wave. Higher neutralizing antibody levels may not reduce Omicron infection risk in third-dose patients. On the contrary, it may be associated with fewer symptoms of infection.