Development of RSV subgroup neutralizing immunity across consecutive seasons with alternating RSV-A and RSV-B predominance

Abstract

Background Respiratory syncytial virus (RSV) circulates as two antigenically distinct subgroups, RSV-A and RSV-B, frequently alternating in seasonal predominance. Whether RSV subgroup predominance affects neutralizing immunity and how population immunity shapes subsequent subgroup dynamics, remains unclear. We analyzed multi-season RSV surveillance data and subgroup neutralizing antibody responses to characterize RSV-A/B neutralizing immunity across age groups and successive seasons. Methods We analyzed 41,899 respiratory samples collected through sentinel surveillance to characterize RSV-A and RSV-B circulation across five seasons (2021–2026). Subgroup neutralization was measured by live-virus neutralization assays in post-season serum samples from infants, children and adults. Results RSV-A and RSV-B alternated in seasonal predominance, with RSV-A predominating in 2021/22 and 2023/24, RSV-B in 2022/23 and 2025/26, with no clear predominance in 2024/25. In infants, the relative neutralizing activity against RSV-A and RSV-B differed across seasons, whereas adults maintained a balanced neutralizing activity against both subgroups. During the first three years of life, repeated exposure broadened antibody responses toward balanced subgroup neutralization. In the 2021/22, 2022/23, and 2024/25 seasons, lower neutralizing activity in infants was observed against the subgroup that predominated in the subsequent RSV epidemic. Conclusions Our findings indicate that neutralizing immunity develops from initially subgroup-biased responses after primary RSV infection toward balanced RSV-A/B neutralization with repeated exposure. Subgroup neutralizing activity in infants varied in the context of alternating RSV-A and RSV-B predominance across successive epidemic seasons. These findings provide new insights into age-dependent and seasonally varying patterns of RSV-A/B neutralizing immunity and subgroup circulation.