Host-mediated selection impacts the diversity of Plasmodium falciparum antigens within infections

Angela M. Early (), Marc Lievens, Bronwyn L. MacInnis, Christian F. Ockenhouse, Sarah K. Volkman, Samuel Adjei, Tsiri Agbenyega, Daniel Ansong, Stacey Gondi, Brian Greenwood, Mary Hamel, Chris Odero, Kephas Otieno, Walter Otieno, Seth Owusu-Agyei, Kwaku Poku Asante, Hermann Sorgho, Lucas Tina, Halidou Tinto, Innocent Valea, Dyann F. Wirth and Daniel E. Neafsey ()
Additional contact information
Angela M. Early: Broad Institute of MIT and Harvard
Marc Lievens: GSK Vaccines
Bronwyn L. MacInnis: Broad Institute of MIT and Harvard
Christian F. Ockenhouse: PATH Malaria Vaccine Initiative
Sarah K. Volkman: Broad Institute of MIT and Harvard
Samuel Adjei: Kwame Nkrumah University of Science and Technology
Tsiri Agbenyega: Kwame Nkrumah University of Science and Technology
Daniel Ansong: Kwame Nkrumah University of Science and Technology
Stacey Gondi: KEMRI–Walter Reed Project
Brian Greenwood: London School of Hygiene and Tropical Medicine
Mary Hamel: KEMRI/CDC Research and Public Health Collaboration
Chris Odero: KEMRI/CDC Research and Public Health Collaboration
Kephas Otieno: KEMRI/CDC Research and Public Health Collaboration
Walter Otieno: KEMRI–Walter Reed Project
Seth Owusu-Agyei: London School of Hygiene and Tropical Medicine
Kwaku Poku Asante: Kintampo Health Research Centre
Hermann Sorgho: Nanoro, Burkina Faso/Institute of Tropical Medicine
Lucas Tina: KEMRI–Walter Reed Project
Halidou Tinto: Nanoro, Burkina Faso/Institute of Tropical Medicine
Innocent Valea: Nanoro, Burkina Faso/Institute of Tropical Medicine
Dyann F. Wirth: Broad Institute of MIT and Harvard
Daniel E. Neafsey: Broad Institute of MIT and Harvard

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: Abstract Host immunity exerts strong selective pressure on pathogens. Population-level genetic analysis can identify signatures of this selection, but these signatures reflect the net selective effect of all hosts and vectors in a population. In contrast, analysis of pathogen diversity within hosts provides information on individual, host-specific selection pressures. Here, we combine these complementary approaches in an analysis of the malaria parasite Plasmodium falciparum using haplotype sequences from thousands of natural infections in sub-Saharan Africa. We find that parasite genotypes show preferential clustering within multi-strain infections in young children, and identify individual amino acid positions that may contribute to strain-specific immunity. Our results demonstrate that natural host defenses to P. falciparum act in an allele-specific manner to block specific parasite haplotypes from establishing blood-stage infections. This selection partially explains the extreme amino acid diversity of many parasite antigens and suggests that vaccines targeting such proteins should account for allele-specific immunity.

Date: 2018
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DOI: 10.1038/s41467-018-03807-7

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