Cross-neutralizing antibody responses among individuals with or without bivalent vaccine: a six-month prospective cohort study

Background/Aims: Although the COVID-19 pandemic has officially ended, SARS-CoV-2 continues to circulate with periodic surges and may exhibit seasonal patterns. Understanding the importance of prompt immunization, particularly in individuals with prior infection, is crucial for developing future vaccination protocols. This study aimed to assess the durability and breadth of neutralizing antibody (nAb) responses against Omicron subvariants based on infection and bivalent vaccination status.Methods: In this six-month prospective cohort study, we evaluated nAb responses to the original SARS-CoV-2 strain (D614G), as well as Omicron subvariants BA.4/5 and XBB.1.5 variants, in 79 healthcare workers stratified by prior Omicron infection and bivalent vaccination status. Blood samples were collected at baseline, 3 months, and 6 months, and nAb titers were measured using an optimized pseudovirus neutralization assay.Results: At 3 months, individuals with prior Omicron infection followed by bivalent vaccination showed significantly higher nAb titers against BA.4/5 and XBB.1.5 compared to those with infection alone or vaccination alone. At 6 months, the highest titers persisted in the group with both prior infection and bivalent vaccination, while titers declined in previously infected but unvaccinated individuals. Notably, individuals with prior infection alone exhibited comparable nAb titers to infection-naïve vaccinated individuals, suggesting limited durability of infection-induced immunity without vaccine-induced boosting.Conclusions: These findings underscore the importance of timely vaccination, even among previously infected individuals, to ensure sustained humoral immunity and broader cross-nAb responses against emerging SARS-CoV-2 variants.