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Multiple Antigen Peptide Vaccines against Plasmodium falciparum Malaria

机译：多种抗恶性疟原虫的抗原肽疫苗

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The multiple antigen peptide (MAP) approach is an effective method to chemically synthesize and deliver multiple T-cell and B-cell epitopes as the constituents of a single immunogen. Here we report on the design, chemical synthesis, and immunogenicity of three Plasmodium falciparum MAP vaccines that incorporated antigenic epitopes from the sporozoite, liver, and blood stages of the life cycle. Antibody and cellular responses were determined in three inbred (C57BL/6, BALB/c, and A/J) strains, one congenic (HLA-A2 on the C57BL/6 background) strain, and one outbred strain (CD1) of mice. All three MAPs were immunogenic and induced both antibody and cellular responses, albeit in a somewhat genetically restricted manner. Antibodies against MAP-1, MAP-2, and MAP-3 had an antiparasite effect that was also dependent on the mouse major histocompatibility complex background. Anti-MAP-1 (CSP-based) antibodies blocked the invasion of HepG2 liver cells by P. falciparum sporozoites (highest, 95.16% in HLA-A2 C57BL/6; lowest, 11.21% in BALB/c). Furthermore, antibodies generated following immunizations with the MAP-2 (PfCSP, PfLSA-1, PfMSP-142, and PfMSP-3b) and MAP-3 (PfRAP-1, PfRAP-2, PfSERA, and PfMSP-142) vaccines were able to reduce the growth of blood stage parasites in erythrocyte cultures to various degrees. Thus, MAP-based vaccines remain a viable option to induce effective antibody and cellular responses. These results warrant further development and preclinical and clinical testing of the next generation of candidate MAP vaccines that are based on the conserved protective epitopes from Plasmodium antigens that are widely recognized by populations of divergent HLA types from around the world.
机译：多抗原肽（MAP）方法是化学合成和递送多个T细胞和B细胞表位作为单个免疫原组成的有效方法。在这里，我们报告了三种恶性疟原虫MAP疫苗的设计，化学合成和免疫原性，这些疫苗掺入了生命周期中子孢子，肝脏和血液阶段的抗原表位。在三只自交系（C57BL / 6，BALB / c和A / J）品系，一个同系（C57BL / 6背景上的HLA-A2）品系和一个外来品系（CD1）的小鼠中确定了抗体和细胞应答。尽管以某种遗传方式限制，所有这三种MAP均为免疫原性并诱导抗体和细胞应答。针对MAP-1，MAP-2和MAP-3的抗体具有抗寄生虫作用，该作用还取决于小鼠主要的组织相容性复合体背景。抗MAP-1（基于CSP）抗体可阻止恶性疟原虫子孢子侵袭HepG2肝细胞（HLA-A2 C57BL / 6中最高，为95.16％; BALB / c中最低，为11.21％）。此外，使用MAP-2（PfCSP，PfLSA-1，PfMSP-142和PfMSP-3b）和MAP-3（PfRAP-1，PfRAP-2，PfSERA和PfMSP-142）疫苗免疫后产生的抗体在不同程度上减少血红细胞培养中血期寄生虫的生长。因此，基于MAP的疫苗仍然是诱导有效抗体和细胞反应的可行选择。这些结果保证了下一代候选MAP疫苗的进一步开发，临床前和临床测试，这些疫苗基于疟原虫抗原的保守保护表位，已被世界各地不同HLA类型人群广泛认可。

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