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Within-infection diversity of Plasmodium falciparum antigens reflects host-mediated selection

Angela M. Early, Marc Lievens, Bronwyn MacInnis, Christian F. Ockenhouse, Sarah K. Volkman, RTS,S Clinical Trial Partnership Committee of Investigators,, Dyann F. Wirth, Daniel E. Neafsey
doi: https://doi.org/10.1101/212209
Angela M. Early
1Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
2Harvard T.H. Chan School of Public Health, Boston, MA, USA
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Marc Lievens
3GSK Vaccines, Rixensart, Belgium
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Bronwyn MacInnis
1Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
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Christian F. Ockenhouse
4PATH Malaria Vaccine Initiative, Washington, DC, USA
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Sarah K. Volkman
1Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
2Harvard T.H. Chan School of Public Health, Boston, MA, USA
5Simmons College, School of Nursing and Health Sciences, Boston, MA, USA
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Dyann F. Wirth
1Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
2Harvard T.H. Chan School of Public Health, Boston, MA, USA
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Daniel E. Neafsey
1Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA
2Harvard T.H. Chan School of Public Health, Boston, MA, USA
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Abstract

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.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted November 01, 2017.
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Within-infection diversity of Plasmodium falciparum antigens reflects host-mediated selection
Angela M. Early, Marc Lievens, Bronwyn MacInnis, Christian F. Ockenhouse, Sarah K. Volkman, RTS,S Clinical Trial Partnership Committee of Investigators,, Dyann F. Wirth, Daniel E. Neafsey
bioRxiv 212209; doi: https://doi.org/10.1101/212209
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Within-infection diversity of Plasmodium falciparum antigens reflects host-mediated selection
Angela M. Early, Marc Lievens, Bronwyn MacInnis, Christian F. Ockenhouse, Sarah K. Volkman, RTS,S Clinical Trial Partnership Committee of Investigators,, Dyann F. Wirth, Daniel E. Neafsey
bioRxiv 212209; doi: https://doi.org/10.1101/212209

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