Optimal vaccination in aging populations under age-dependent infection fatality risks

Abstract Background Vaccination programs have greatly reduced the burden of infectious diseases, particularly in childhood. As populations age, however, the burden of respiratory infections such as influenza A, respiratory syncytial virus (RSV), and SARS-CoV-2 increasingly falls on older adults. Because infection fatality rates rise steeply with age, vaccination strategies that alter the age distribution of infections may have complex population-level consequences. We used transmission models to examine how the timing and frequency of vaccination influence infection-induced mortality and years of life lost (YLL) in aging populations. Methods and findings We analyzed age-structured transmission models that incorporate demographic change, age-specific infection fatality rates, and waning immunity after infection or vaccination. We varied the age at first vaccination, vaccination intervals, and coverage across a wide range of pathogen characteristics, including transmissibility and the duration of natural and vaccine-induced immunity. For single-dose vaccination programs with long-lived protection (5–50 years), the age at vaccination minimizing mortality in older adults for pathogens with strongly age-increasing fatality risk typically ranges from 60 to 80 years. The optimal age shifted toward older ages when transmissibility was higher or natural immunity lasted longer. Repeated vaccination produced qualitatively different outcomes. When vaccine-induced immunity was short-lived ( < 5 years), vaccination can shift infections toward the oldest ages where fatality risks are highest, increasing both mortality and YLL compared with no vaccination. This study has limitations. Our analysis used stylized transmission models and assumed vaccines that fully prevent infection, which may overestimate age-shifting effects compared with real-world vaccines that primarily reduce disease severity. Conclusions Optimal adult vaccination strategies depend jointly on pathogen transmissibility, the duration of immunity, and population demography. Vaccination programs that suppress infections earlier in life without protecting individuals into late life may shift infections toward ages with higher fatality risk. These findings highlight the need to evaluate adult vaccination strategies across the full life course and have important implications for vaccination policies against influenza A and other pathogens with strongly age-dependent infection fatality rates. Author Summary Why was this study done? Populations worldwide are aging rapidly, increasing the burden of respiratory infections such as influenza A, respiratory syncytial virus (RSV), and SARS-CoV-2 in older adults. Vaccination of adults is therefore becoming an increasingly important public health strategy. However, there are no general principles for deciding at which ages vaccination should be offered. What did the researchers do and find? We used mathematical transmission models to examine how the timing and frequency of vaccination influence infection-related mortality in aging populations. We found that the optimal age for vaccination depends strongly on pathogen characteristics such as transmissibility and the duration of immunity. In some situations, vaccination can even increase mortality by shifting infections to older ages where fatality risks are highest. What do these findings mean? These results show that there is no universal rule for the optimal timing of adult vaccination. Vaccination strategies should account for how vaccination changes the age distribution of infections over the life course. Our findings provide guidance for designing vaccination strategies against influenza A and other pathogens in aging societies.