Real-World Effectiveness of Sequential Pneumococcal Vaccination in Older Adults: A Cohort Study

Abstract Background While the real-world effectiveness of various pneumococcal vaccine formulations has been individually evaluated, comparative evaluations of 13-valent pneumococcal conjugate vaccine (PCV13)/23-valent pneumococcal polysaccharide vaccine (PPSV23) and combinations thereof are limited. We evaluated the real-world vaccine effectiveness of PCV13 alone, PPSV23 alone, or PCV13 followed by PPSV23 amongst older adults. Methods A population-based retrospective cohort study, including all adult Singaporeans aged ≥65 to 89 years from 1 January 2020 to 31 July 2024. The time to event from cohort enrollment to pneumococcal-related disease and all-cause pneumonia was measured, considering death as a competing risk. Cox regression models were used to estimate cause-specific hazards, with PCV13 alone, PPSV23 alone, and PCV13 followed by PPSV23 incorporated into models as time-dependent covariates. Vaccination status was assessed using the National Immunisation Registry; outcomes were identified using national healthcare claims data. Results A total of 656 337 older Singaporeans were included; 348 831 (53.1%) remained unvaccinated by the study end date. Sequential PCV13 followed by PPSV23 significantly protected against pneumococcal-related disease (adjusted hazard ratio, 0.22 [95% confidence interval, .06–.76]), pneumonia hospitalizations (0.94 [.91–.97]), and all-cause mortality (0.70 [.67–.74]). While PCV13 alone also reduced the risk of pneumonia hospitalization (adjusted hazard ratio, 0.96 [95% CI, .92–.99]) and all-cause mortality (0.86 [95% confidence interval, .83–.89]), vaccine effectiveness estimates were numerically lower than with sequential vaccination. For sequential vaccination, no significant waning of protection against all-cause pneumonia hospitalization or death was observed; a longer time interval (≥365 days) between PCV13 and PPSV23 was associated with a numerically lower risk of all-cause pneumonia hospitalization or death than a shorter interval (<365 days). Conclusions PCV13 followed by PPSV23 was associated with lower risk of pneumococcal-related disease, pneumonia, and all-cause mortality, supporting recommendations for sequential vaccination in older adults.