Effects of epistasis and recombination between vaccine-escape and virulence alleles on the dynamics of pathogen adaptation

Modelling shows that vaccines that reduce infection or hasten infection clearance generate positive epistasis between vaccine-escape and virulence alleles, whereas vaccines that reduce virulence generate negative epistasis. High rates of recombination also affect how selection acts on both alleles. Pathogen adaptation to public health interventions such as vaccination may take tortuous routes and involve multiple mutations at different locations in the pathogen genome, acting on distinct phenotypic traits. Yet how these multi-locus adaptations jointly evolve is poorly understood. Here we consider the joint evolution of two adaptations: pathogen escape from the vaccine-induced immune response and adjustments to pathogen virulence affecting transmission or clearance. We elucidate the role played by epistasis and recombination, with an emphasis on the different protective effects of vaccination. We show that vaccines blocking infection, reducing transmission and/or increasing clearance generate positive epistasis between the vaccine-escape and virulence alleles, favouring strains that carry both mutations, whereas vaccines reducing virulence mortality generate negative epistasis, favouring strains that carry either mutation but not both. High rates of recombination can affect these predictions. If epistasis is positive, frequent recombination can prevent the transient build-up of more virulent escape strains. If epistasis is negative, frequent recombination between loci can create an evolutionary bistability, favouring whichever adaptation is more accessible. Our work provides a timely alternative to the variant-centred perspective on pathogen adaptation and captures the effect of different types of vaccine on the interference between multiple adaptive mutations.

Automated summary

This study investigates the joint evolution mechanism of pathogen adaptation to vaccine-induced immune response and pathogen virulence, with a focus on the protective effects of vaccines. The research reveals that vaccines that block infection, reduce transmission, and/or increase clearance generate positive epistasis between vaccine-escape and virulence alleles, while vaccines that reduce mortality generate negative epistasis. High rates of recombination can also affect these predictions.