In silico characterisation of putative Plasmodium falciparum vaccine candidates in African malaria populations

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作者
O. Ajibola
M. F. Diop
A. Ghansah
L. Amenga-Etego
L. Golassa
T. Apinjoh
M. Randrianarivelojosia
O. Maiga-Ascofare
W. Yavo
M. Bouyou-Akotet
K. M. Oyebola
B. Andagalu
U. D’Alessandro
D. Ishengoma
A. A. Djimde
E. Kamau
A. Amambua-Ngwa
机构
[1] The Gambia at London School of Hygiene and Tropical Medicine,Medical Research Council Unit
[2] First Technical University,Noguchi Memorial Institute for Medical Research
[3] University of Ghana,West African Center for Cell Biology of Infectious Pathogens
[4] University of Ghana,Aklilu Lemma Institute of Pathobiology
[5] Addis Ababa University,Department of Biochemistry and Molecular Biology
[6] University of Buea,Unite Des Sciences Pharmaceutiques et Biologiques
[7] Institut Pasteur of Madagascar,Faculty of Medicine
[8] Bernhard Nocht Institute for Topical Medicine (BNITM),Department of Zoology
[9] University Félix Houphouët-Boigny,United States Army Medical Research Directorate
[10] University of Health Sciences,Africa
[11] University of Lagos,Malaria Research and Training Centre
[12] Kenya Medical Research Institute/Walter Reed Project,Department of Pathology and Laboratory Medicine, David Geffen School of Medicine
[13] National Institute for Medical Research (NIMR),U.S. Military HIV Research Program
[14] University of Science,undefined
[15] Techniques and Technologies of Bamako,undefined
[16] University of California,undefined
[17] Walter Reed Army Institute of Research,undefined
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摘要
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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