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Abstract
Genetic diversity of surface exposed and stage specific Plasmodium falciparum immunogenic proteins pose a major roadblock to developing an effective malaria vaccine with broad and long-lasting immunity. We conducted a prospective genetic analysis of candidate antigens (msp1, ama1, rh5, eba175, glurp, celtos, csp, lsa3, Pfsea, trap, conserved chrom3, hyp9, hyp10, phistb, surfin8.2, and surfin14.1) for malaria vaccine development on 2375 P. falciparum sequences from 16 African countries. We described signatures of balancing selection inferred from positive values of Tajima’s D for all antigens across all populations except for glurp. This could be as a result of immune selection on these antigens as positive Tajima’s D values mapped to regions with putative immune epitopes. A less diverse phistb antigen was characterised with a transmembrane domain, glycophosphatidyl anchors between the N and C- terminals, and surface epitopes that could be targets of immune recognition. This study demonstrates the value of population genetic and immunoinformatic analysis for identifying and characterising new putative vaccine candidates towards improving strain transcending immunity, and vaccine efficacy across all endemic populations.
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1 The Gambia at London School of Hygiene and Tropical Medicine, Medical Research Council Unit, Banjul, The Gambia (GRID:grid.415063.5) (ISNI:0000 0004 0606 294X); First Technical University, Ibadan, Nigeria (GRID:grid.510438.b)
2 The Gambia at London School of Hygiene and Tropical Medicine, Medical Research Council Unit, Banjul, The Gambia (GRID:grid.415063.5) (ISNI:0000 0004 0606 294X)
3 University of Ghana, Noguchi Memorial Institute for Medical Research, Legon, Ghana (GRID:grid.8652.9) (ISNI:0000 0004 1937 1485)
4 University of Ghana, West African Center for Cell Biology of Infectious Pathogens, Accra, Ghana (GRID:grid.8652.9) (ISNI:0000 0004 1937 1485)
5 Addis Ababa University, Aklilu Lemma Institute of Pathobiology, Addis Ababa, Ethiopia (GRID:grid.7123.7) (ISNI:0000 0001 1250 5688)
6 University of Buea, Department of Biochemistry and Molecular Biology, Buea, Cameroon (GRID:grid.29273.3d) (ISNI:0000 0001 2288 3199)
7 Institut Pasteur of Madagascar, Antanarivo, Madagascar (GRID:grid.418511.8) (ISNI:0000 0004 0552 7303)
8 Bernhard Nocht Institute for Topical Medicine (BNITM), Hamburg, Germany (GRID:grid.424065.1) (ISNI:0000 0001 0701 3136)
9 University Félix Houphouët-Boigny, Unite Des Sciences Pharmaceutiques et Biologiques, Abidjan, Côte d’Ivoire (GRID:grid.410694.e) (ISNI:0000 0001 2176 6353)
10 University of Health Sciences, Faculty of Medicine, Libreville, Gabon (GRID:grid.502965.d)
11 University of Lagos, Department of Zoology, Lagos, Nigeria (GRID:grid.411782.9) (ISNI:0000 0004 1803 1817)
12 Kenya Medical Research Institute/Walter Reed Project, United States Army Medical Research Directorate-Africa, Kisumu, Kenya (GRID:grid.33058.3d) (ISNI:0000 0001 0155 5938)
13 National Institute for Medical Research (NIMR), Tanga, Tanzania (GRID:grid.416716.3) (ISNI:0000 0004 0367 5636)
14 University of Science, Techniques and Technologies of Bamako, Malaria Research and Training Centre, Bamako, Mali (GRID:grid.461088.3) (ISNI:0000 0004 0567 336X)
15 University of California, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, Los Angeles, USA (GRID:grid.19006.3e) (ISNI:0000 0000 9632 6718); Walter Reed Army Institute of Research, U.S. Military HIV Research Program, Silver Spring, USA (GRID:grid.507680.c) (ISNI:0000 0001 2230 3166)