Diversity of vaccination-induced immune responses can prevent the spread of vaccine escape mutants

Pathogens that are resistant against drug treatment are widely observed. In contrast, pathogens that escape the immune response elicited upon vaccination are rare. Previous studies showed that the prophylactic character of vaccines, the multiplicity of epitopes to which the immune system responds within a host, and their diversity between hosts delay the evolution and emergence of escape mutants in a vaccinated population. By extending previous mathematical models, we find that, depending on the cost of the escape mutations, there even exist critical levels of immune response diversity that completely prevent vaccine escape. Furthermore, to quantify the potential for vaccine escape below these critical levels, we propose a concept of escape depth which measures the fraction of escape mutants that can spread in a vaccinated population. Determining this escape depth for a vaccine could help to predict its sustainability in the face of pathogen evolution.