Mosaic vaccination: How distributing different vaccines across a population could improve epidemic control

Although vaccination has been remarkably effective against some pathogens, for others, rapid antigenic evolution results in vaccination conferring only weak and/or short‐lived protection. Consequently, considerable effort has been invested in developing more evolutionarily robust vaccines, either by targeting highly conserved components of the pathogen (universal vaccines) or by including multiple immunological targets within a single vaccine (multi‐epitope vaccines). An unexplored third possibility is to vaccinate individuals with one of a number of qualitatively different vaccines, creating a “mosaic” of individual immunity in the population. Here we explore whether a mosaic vaccination strategy can deliver superior epidemiological outcomes to “conventional” vaccination, in which all individuals receive the same vaccine. We suppose vaccine doses can be distributed between distinct vaccine “targets” (e.g., different surface proteins against which an immune response can be generated) and/or immunologically distinct variants at these targets (e.g., strains); the pathogen can undergo antigenic evolution at both targets. Using simple mathematical models, here we provide a proof‐of‐concept that mosaic vaccination often outperforms conventional vaccination, leading to fewer infected individuals, improved vaccine efficacy, and lower individual risks over the course of the epidemic.