Plasmodium falciparum causes the most severe form of malaria disease and is the major cause of infection-related mortalities in the world. Due to increasing in P. falciparum resistance to the first-line antimalarial drugs, an effective vaccine for the control and elimination of malaria infection is urgent. Because the pathogenesis of malaria disease results from blood-stage infection, and all of the symptoms and clinical illness of malaria occur during this stage, there is a strong rationale to develop vaccine against this stage. In the present study, different structural-vaccinology and immuno informatics tools were applied to design an effective antibody-inducing multi-epitope vaccine against the blood-stage of P. falciparum. The designed multi-epitope vaccine was composed of three main parts including B cell epitopes, T helper (Th) cell epitopes, and two adjuvant motives (HP91 and RS09), which were linked to each other via proper linkers. B cell and T cell epitopes were derived from four protective antigens expressed on the surface of merozoites, which are critical to invade the erythrocytes. HP91 and RS09 adjuvants and Th cell epitopes were used to induce, enhance and direct the best form of humoral immune-response against P. falciparum surface merozoite antigens. The vaccine construct was modeled, and after model quality evaluation and refinement by different software, the high-quality 3D-structure model of the vaccine was achieved. Analysis of immunological and physicochemical features of the vaccine showed acceptable results. We believe that this multi-epitope vaccine can be effective for preventing malaria disease caused by P. falciparum.

恶性疟原虫引起最严重的疟疾形式，并且是世界上与感染有关的死亡率的主要原因。由于恶性疟原虫对一线抗疟药的抗药性增加，控制和消除疟疾感染的有效疫苗迫在眉睫。由于疟疾的发病机理是由血液阶段的感染引起的，并且疟疾的所有症状和临床疾病都在此阶段发生，因此有很强的理由开发针对该阶段的疫苗。在本研究中，不同的结构疫苗学和免疫信息学工具被用于设计针对恶性疟原虫血液阶段的有效的抗体诱导多表位疫苗。设计的多表位疫苗由三个主要部分组成，包括B细胞表位，T辅助（Th）细胞表位和两个佐剂动机（HP91和RS09），它们通过适当的接头相互连接。B细胞和T细胞表位衍生自裂殖子表面表达的四种保护性抗原，这对侵入红细胞至关重要。HP91和RS09佐剂和Th细胞表位被用来诱导，增强和指导针对恶性疟原虫的体液免疫反应的最佳形式表面裂殖子抗原。对疫苗构建体进行建模，并通过不同软件对模型质量进行评估和完善，从而获得了疫苗的高质量3D结构模型。疫苗的免疫和理化特征分析显示可接受的结果。我们相信，这种多表位疫苗可以有效预防由恶性疟原虫引起的疟疾。