Inferring vaccine efficacy and mode of action from human challenge studies

To assess the long-term effect of a vaccination programme, understanding both the efficacy and the mode of action of the vaccine is crucial. The actual mode of action is difficult to infer from field trials, because of the heterogeneity of exposure to infection. Here we show an approach to determine both vaccine efficacy and the mode of action of vaccines from human challenge studies. Our approach reveals how vaccines alter an individual’s susceptibility, and identifies a mixture of different modes of action as a function of the challenged dose. By applying the proposed method to influenza challenge data, we illustrate that potentially the lowest vaccine efficacy may occur at intermediate doses, suggesting a hypothesis that moderate transmission intensities might be optimal for establishing infections in vaccinated individuals. One sentence summary Human challenge studies reveal the protection mechanism of vaccines by measuring variation in susceptibility to infection.