TY - JOUR T1 - Within-infection diversity of <em>Plasmodium falciparum</em> antigens reflects host-mediated selection JF - bioRxiv DO - 10.1101/212209 SP - 212209 AU - Angela M. Early AU - Marc Lievens AU - Bronwyn MacInnis AU - Christian F. Ockenhouse AU - Sarah K. Volkman AU - RTS,S Clinical Trial Partnership Committee of Investigators, AU - Dyann F. Wirth AU - Daniel E. Neafsey Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/11/01/212209.abstract N2 - Host immunity exerts strong selection on pathogens, but it does not act in a uniform manner across individual hosts. By providing a direct approach for understanding host-specific selection pressures, patterns of intra-host pathogen diversity complement population genetic analyses performed on broad geographic scales. Here, we perform a combined analysis of inter- and intra-host diversity for the malaria parasite Plasmodium falciparum with haplotype sequences of three antigens sampled from over 4,500 natural infections in sub-Saharan Africa using targeted deep sequencing. We find that multi-strain infections in young children contain non-random combinations of parasite genotypes, and identify individual amino acid positions that may contribute to strain-specific blocking of infections. These results demonstrate for the first time that natural host defenses to Plasmodium detectably impact which infections proceed to the blood stage within a given host. This selection partially explains the extreme amino acid diversity observed at many parasite antigens and suggests that vaccines targeting such proteins should account for the impact of allele-specific immunity. ER -