Molecular Biology and Immunology Department, Fundación Instituto de Immunología de Colombia (FIDIC), Bogotá D.C., Colombia.
MSc Programme in Microbiology, Universidad Nacional de Colombia, Bogotá D.C., Colombia.
PLoS One. 2018 Sep 10;13(9):e0203715. doi: 10.1371/journal.pone.0203715. eCollection 2018.
Malaria is an infectious disease caused by parasites from the genus Plasmodium (P. falciparum and P. vivax are responsible for 90% of all clinical cases); it is widely distributed throughout the world's tropical and subtropical regions. The P. vivax Pv12 protein is involved in invasion, is expressed on merozoite surface and has been recognised by antibodies from individuals exposed to the disease. In this study, B- and T-cell epitopes from Pv12 were predicted and characterised to advance in the design of a peptide-based vaccine against malaria. For evaluating the humoral response of individuals exposed to natural P. vivax infection from two endemic areas in Colombia, BepiPred-1.0 software was used for selecting B-cell epitopes. B-cell epitope 39038 displayed the greatest recognition by naturally-acquired antibodies and induced an IgG2/IgG4 response. NetMHCIIpan-3.1 prediction software was used for selecting peptides having high affinity binding for HLA-DRβ1* allele lineages and this was confirmed by in-vitro binding assays. T-epitopes 39113 and 39117 triggered a memory T-cell response (Stimulation Index≥2) and significant cytokine production. Combining in-silico, in-vitro and functional assays, two Pv12 protein regions (containing peptides 39038, 39040, 39113 and 39117) have thus been characterised as promising vaccine candidates against P. vivax malaria.
疟疾是一种由疟原虫属寄生虫引起的传染病(恶性疟原虫和间日疟原虫负责所有临床病例的 90%);它广泛分布在世界的热带和亚热带地区。Pv12 蛋白参与入侵,表达在裂殖子表面,已被暴露于该疾病的个体的抗体识别。在这项研究中,预测和鉴定了 Pv12 的 B 细胞和 T 细胞表位,以推进疟疾肽疫苗的设计。为了评估来自哥伦比亚两个流行地区自然感染间日疟原虫的个体的体液反应,使用 BepiPred-1.0 软件选择 B 细胞表位。B 细胞表位 39038 显示了最大的被自然获得的抗体识别,并诱导 IgG2/IgG4 反应。NetMHCIIpan-3.1 预测软件用于选择与 HLA-DRβ1*等位基因系具有高亲和力结合的肽,这通过体外结合测定得到了证实。T 表位 39113 和 39117 触发了记忆 T 细胞反应(刺激指数≥2)和显著的细胞因子产生。通过计算机模拟、体外和功能测定相结合,已经鉴定了 Pv12 蛋白的两个区域(包含肽 39038、39040、39113 和 39117)作为间日疟原虫疟疾有前途的疫苗候选物。