Characterization of Plasmodium falciparum Proteome at Asexual Blood Stages for Screening of Effective Vaccine Candidates: An Immunoinformatics Approach

S. P. Singh, V. Verma, B. Mishra
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引用次数: 9

Abstract

Malaria is a complex parasitic disease that is currently causing great concerns globally owing to the resistance to antimalarial drugs and lack of an effective vaccine. The present study involves the characterization of extracellular secretory proteins as vaccine candidates derived from proteome analysis of Plasmodium falciparum at asexual blood stages of malaria. Among the screened 32 proteins, 31 were predicted as antigens by the VaxiJen program, and 26 proteins had less than two transmembrane spanning regions predicted using the THMMM program. Moreover, 10 and 5 proteins were predicted to contain secretory signals by SignalP and TargetP, respectively. T-cell epitope prediction using MULTIPRED2 and NetCTL programs revealed that most of the predicted antigens are immunogenic and contain more than 10% supertype and 5% promiscuous epitopes of HLA-A, -B, or -DR. We anticipate that T-cell immune responses against asexual blood stages of Plasmodium are dispersed on a relatively large number of parasite antigens. This is the first report, to the best of our knowledge, offering new insights, at the proteome level, for the putative screening of effective vaccine candidates against the malaria pathogen. The findings also suggest new ways forward for the modern omics-guided vaccine target discovery using reverse vaccinology.
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恶性疟原虫蛋白质组在无性血阶段的特征,筛选有效的候选疫苗:免疫信息学方法
疟疾是一种复杂的寄生虫病,目前由于抗疟疾药物的耐药性和缺乏有效的疫苗,在全球引起极大关注。目前的研究涉及细胞外分泌蛋白作为候选疫苗的特性,这些蛋白来自于疟疾无性血期恶性疟原虫的蛋白质组学分析。在筛选的32个蛋白中,31个蛋白通过VaxiJen程序预测为抗原,26个蛋白使用THMMM程序预测的跨膜跨越区域少于两个。此外,通过SignalP和TargetP分别预测了10个和5个蛋白含有分泌信号。使用MULTIPRED2和NetCTL程序进行t细胞表位预测显示,大多数预测抗原具有免疫原性,含有超过10%的HLA-A、-B或-DR的超型和5%的混杂表位。我们预计,针对疟原虫无性血期的t细胞免疫反应分散在相对大量的寄生虫抗原上。据我们所知,这是第一份在蛋白质组水平上为推定筛选有效的疟疾病原体候选疫苗提供新见解的报告。这些发现也为利用反向疫苗学在现代组学指导下发现疫苗靶点提供了新的途径。
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