Natural Boosting and the Immunogenicity of the XBB.1.5 Monovalent Vaccine in the Coronavirus Disease 2019 Endemic Era: A Longitudinal Observational Study.

This article focuses on the longitudinal assessment of group immunity against COVID-19 during the transition from pandemic to endemic phases, with particular attention to the effects of breakthrough infections (BIs), natural boosting (NB), and the updated XBB.1.5 monovalent vaccine (MonoV). A multicenter cohort of 327 healthcare workers in South Korea was followed from March 2021 to December 2023, revealing that anti-spike protein antibody levels declined in the pre-Omicron era, were maintained during the Omicron era due to BIs, and increased in the endemic era largely through NB. The study found that the XBB.1.5 MonoV significantly enhanced neutralizing antibody activity not only against the vaccine strain but also against the subsequent epidemic JN.1 strain, outperforming the previous wild-type BA.4/5 bivalent vaccine. These findings suggest that while natural boosting contributes to sustained immunity in the endemic phase, updated vaccinations like the MonoV remain important for robust protection against emerging SARS-CoV-2 variants.