Optimal seasonal timing of infant immunization to prevent RSV hospitalizations in Japan: a modelling study

Abstract The seasonal circulation of respiratory syncytial virus (RSV) in countries such as Japan, together with the transient nature of passive immunity conferred to infants via maternal vaccination or monoclonal antibody administration, may warrant a differential strategy for those born during the RSV inter-seasonal period. Maximal effectiveness may be achieved by deferring immunisation of this cohort from birth until entry into their first RSV season using catch-up administration of monoclonal antibody through a seasonal and catch-up programme, compared with year-round administration. To estimate the benefit of seasonal and catch-up programmes in reducing RSV infant hospitalisations in Japan, we developed a static cohort model following infants through their first year of life, parameterised by Japanese data on weekly and municipality-specific RSV incidence during 2018 to 2025 and on RSV case hospitalisation risk from a health claims database study. We used Bayesian inference to estimate the effectiveness and its waning for maternal vaccine (RSVpreF) and long-acting monoclonal antibody (nirsevimab) from trial data. We estimate that year-round programme of RSVpreF or nirsevimab could reduce RSV hospitalisations from the status quo, under which only high-risk infants are eligible for monoclonal antibodies, by 46% (95% uncertainty range (UR): 31%, 65%) or 58% (95%UR: 39%, 79%) respectively. Seasonal and catch-up programmes could achieve percentage reductions of 1.1-fold (95%UR: 0.82, 1.6) or 0.98-fold (95%UR: 0.83, 1.2) compared with the year-round programme. If seasonality matches the seasonal immunisation timing, using 2024 as an example, the percentage reduction was 1.2-fold (95%UR: 0.95, 1.6) or 1.1-fold (95%UR: 0.97, 1.2), respectively, compared with the year-round programme. If protection from nirsevimab remained substantial after six months, the year-round programme would likely to be more effective. RSVpreF and nirsevimab may substantially reduce RSV infant hospitalisations in Japan. The benefit of the seasonal programmes depends on predictability of RSV seasonality and potential logistical challenges.