Syracuse

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

Archive ouverte

Mcleod, David, V | Gandon, Sylvain

Edité par CCSD ; Nature -

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

• Description
• Sujet/Public
• Outil
• Outil d'anticipation
• Mémoire et thèse
• Gestion