Abstract
Significance The ongoing pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) raises an important question: who should we vaccinate first? Answering this question requires an analysis of both the short-term (epidemiological) and the long-term (evolutionary) consequences of targeted vaccination strategies. We analyze the speed of pathogen adaptation and the cumulative number of deaths in heterogeneous host populations to shed light on the effects of alternative vaccination strategies. This analysis shows that minimizing the speed of pathogen adaptation does not always minimize the number of deaths. This evaluation of both the epidemiological and evolutionary consequences of public health policies provides a practical tool to identify the best vaccination strategy.