Medical Research Council Unit, The Gambia at London School of Hygiene and Tropical Medicine, Banjul, The Gambia.
First Technical University, Ibadan, Nigeria.
Sci Rep. 2021 Aug 10;11(1):16215. doi: 10.1038/s41598-021-95442-4.
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.
表面暴露和阶段特异性疟原虫免疫原性蛋白的遗传多样性对开发具有广泛和持久免疫力的有效疟疾疫苗构成了重大障碍。我们对来自 16 个非洲国家的 2375 个疟原虫序列进行了候选抗原（msp1、ama1、rh5、eba175、glurp、celtos、csp、lsa3、Pfsea、trap、保守 chrom3、hyp9、hyp10、phistb、surfin8.2 和 surfin14.1）的前瞻性遗传分析，以用于疟疾疫苗的开发。除了 glurp 之外，我们描述了所有抗原在所有人群中都存在正 Tajima's D 值所推断出的平衡选择特征。这可能是由于这些抗原受到免疫选择的影响，因为正 Tajima's D 值映射到具有潜在免疫表位的区域。phistb 抗原的多样性较低，具有跨膜结构域、N 和 C 末端之间的糖磷脂锚，以及可能成为免疫识别目标的表面表位。这项研究表明，群体遗传和免疫信息学分析对于识别和表征新的潜在疫苗候选物具有重要价值，可以提高跨越所有流行人群的菌株免疫和疫苗效力。
