Multiscale Immune Selection and the Transmission-Diversity Feedback in Antigenically Diverse Pathogen Systems

Am Nat. 2018 Dec;192(6):E189-E201. doi: 10.1086/699535. Epub 2018 Sep 5.


Antigenic diversity is commonly used by pathogens to enhance their transmission success. Within-host clonal antigenic variation helps to maintain long infectious periods, whereas high levels of allelic diversity at the population level significantly expand the pool of susceptible individuals. Diversity, however, is not necessarily a static property of a pathogen population but in many cases is generated by the very act of infection and transmission, and it is therefore expected to respond dynamically to changes in transmission and immune selection. We hypothesized that this coupling creates a positive feedback whereby infection and disease transmission promote the generation of diversity, which itself facilitates immune evasion and further infections. To investigate this link in more detail, we considered the human malaria parasite Plasmodium falciparum, one of the most important antigenically diverse pathogens. We developed an individual-based model in which antigenic diversity emerges as a dynamic property from the underlying transmission processes. Our results show that the balance between stochastic extinction and the generation of new antigenic variants is intrinsically linked to within-host and between-host immune selection. This in turn determines the level of diversity that can be maintained in a given population. Furthermore, the transmission-diversity feedback can lead to temporal lags in the response to natural or intervention-induced perturbations in transmission rates. Our results therefore have important implications for monitoring and assessing the effectiveness of disease control efforts.

Keywords: Plasmodium falciparum; antigenic diversity; immune selection; individual-based model; positive feedback; recombination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Antigenic Variation / genetics
  • Antigenic Variation / physiology*
  • Female
  • Host-Parasite Interactions / immunology
  • Humans
  • Malaria, Falciparum / epidemiology
  • Malaria, Falciparum / immunology*
  • Malaria, Falciparum / transmission
  • Male
  • Models, Theoretical
  • Mosquito Vectors / parasitology
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / immunology*