Considerations in the deployment of novel universal vaccines against epidemic and pandemic influenza

There is increasing interest in the development of new, ‘universal’ influenza vaccines (UIV) that - unlike current vaccines - are effective against a broad range of seasonal influenza strains, as well as against novel pandemic viruses. Even where these vaccines do not block infection, they can moderate clinical severity, reducing morbidity and mortality while potentially also reducing opportunities for transmission. Previous modelling studies have illustrated the potential epidemiological benefits of UIVs, including their potential to mitigate pandemic burden. However, these new vaccines could shape population immunity in complex ways. Here, using mathematical models of influenza transmission, we illustrate two types of unintended consequences that could arise from their future deployment. First, by reducing the amount of infection-induced immunity in a population without fully replacing it, a seasonal UIV programme may permit larger pandemics than in the absence of vaccination. Second, the more successful a future UIV programme is in reducing transmission of seasonal influenza, the more vulnerable the population could become to the emergence of a vaccine-escape variant. These risks could be mitigated by optimal deployment of any future UIV vaccine: namely, the use of a combined vaccine formulation (incorporating conventional as well as multiple universal antigenic targets), and by achieving sufficient population coverage to compensate for reductions in infection-induced immunity. As early candidates of UIVs approach advanced clinical trials, there is a need to monitor their characteristics in such a way that is focused on their potential impact. This work offers a first step in this direction.