Malaria vaccine candidate: design of a multivalent subunit α-helical coiled coil poly-epitope.
Malaria vaccine candidate: design of a multivalent subunit α-helical coiled coil poly-epitope.
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DOI：
10.1016/j.vaccine.2011.06.122
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发表时间：
2011-09-16
期刊：
影响因子：
5.5
通讯作者：
Corradin, Giampietro
中科院分区：
文献类型：
--
作者：
Olugbile, Sope;Villard, Viviane;Bertholet, Sylvie;Jafarshad, Ali;Kulangara, Caroline;Roussilhon, Christian;Frank, Geraldine;Agak, George W.;Felger, Ingrid;Nebie, Issa;Konate, Karidia;Kajava, Andrey V.;Schuck, Peter;Druilhe, Pierre;Spertini, Francois;Corradin, Giampietro
先前描述了一种基于蛋白质结构基序快速鉴定新疟疾抗原的新策略。我们鉴定并评价了几种含有α-螺旋卷曲螺旋蛋白基序的疟疾抗原片段的疟疾疫苗潜力。通过利用这些结构片段的相对短的尺寸，我们构建了不同的多表位，其中这些片段中的3个或4个通过非免疫原性接头连接在一起。仅掺入作为具有抗寄生虫体外生物活性的人抗体的靶标的肽。其中一个构建体，P181，被生活在疟疾流行区的成年人的血清和外周血单核细胞（PBMC）很好地识别。亲和纯化的抗原特异性人抗体和血清从P181免疫小鼠识别天然蛋白质的疟疾感染的红细胞在免疫荧光和蛋白质印迹分析。此外，在抗体依赖性细胞抑制（ADCI）测定中，特异性抗体抑制寄生虫发育。在塞内加尔的纵向随访研究中，自然诱导的抗原特异性人抗体滴度很高，与疟疾的临床保护有关。
A new strategy for the rapid identification of new malaria antigens based on protein structural motifs was previously described. We identified and evaluated the malaria vaccine potential of fragments of several malaria antigens containing α-helical coiled coil protein motifs. By taking advantage of the relatively short size of these structural fragments, we constructed different poly-epitopes in which 3 or 4 of these segments were joined together via a non-immunogenic linker. Only peptides that are targets of human antibodies with anti-parasite in vitro biological activities were incorporated. One of the constructs, P181, was well recognized by sera and peripheral blood mononuclear cells (PBMC) of adults living in malaria-endemic areas. Affinity purified antigen-specific human antibodies and sera from P181-immunized mice recognised native proteins on malaria-infected erythrocytes in both immunofluorescence and western blot assays. In addition, specific antibodies inhibited parasite development in an antibody dependent cellular inhibition (ADCI) assay. Naturally induced antigen-specific human antibodies were at high titers and associated with clinical protection from malaria in longitudinal follow-up studies in Senegal.
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