Leaky protection reveals three patterns in the relative advantages of vaccination strategies across transmission intensity

Abstract

Targeted vaccination often prioritizes individuals who contribute most to transmission. However, this rationale may change under leaky protection, whereby vaccination reduces susceptibility at each exposure rather than fully preventing infection. Here, we use a survey-derived individual-level exposure framework for 2,279 residents to simulate infection dynamics across ranges of transmission intensity and vaccine efficacy. We compare two vaccination strategies: the high-exposure strategy (prioritizing highly exposed individuals) and the oldest-first strategy (prioritizing older individuals). As transmission intensity changes, we identify three patterns in the relative advantages of these two strategies. At low transmission, the high-exposure strategy outperforms the oldest-first strategy in reducing both epidemic peak size and final infection proportion. At intermediate transmission, it lowers epidemic peak size but increases final infection proportion, revealing a trade-off between these metrics. At high transmission, differences between the strategies narrow, and the oldest-first strategy has a slight advantage for both metrics. Overall, our findings highlight the importance of considering vaccine failure mode when evaluating vaccination policies under different transmission dynamics.