Emory Vaccine Center, YerkesNational Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA.
Division of Infectious Diseases, Department of Medicine, Emory University, 69 Jesse Hill, Jr. Drive, SE, Atlanta, GA 30303, USA.
Sci Rep. 2016 Oct 6;6:34527. doi: 10.1038/srep34527.
The most widespread Plasmodium species, Plasmodium vivax, poses a significant public health threat. An effective vaccine is needed to reduce global malaria burden. Of the erythrocytic stage vaccine candidates, the 19 kDa fragment of the P. vivax Merozoite Surface Protein 1 (PvMSP1) is one of the most promising. Our group has previously defined several promiscuous T helper epitopes within the PvMSP1 protein, with features that allow them to bind multiple MHC class II alleles. We describe here a P. vivax recombinant modular chimera based on MSP1 (PvRMC-MSP1) that includes defined T cell epitopes genetically fused to PvMSP1. This vaccine candidate preserved structural elements of the native PvMSP1 and elicited cytophilic antibody responses, and CD4+ and CD8+ T cells capable of recognizing PvMSP1. Although CD8+ T cells that recognize blood stage antigens have been reported to control blood infection, CD8+ T cell responses induced by P. falciparum or P. vivax vaccine candidates based on MSP1 have not been reported. To our knowledge, this is the first time a protein based subunit vaccine has been able to induce CD8+ T cell against PvMSP1. The PvRMC-MSP1 protein was also recognized by naturally acquired antibodies from individuals living in malaria endemic areas with an antibody profile associated with protection from infection. These features make PvRMC-MSP1 a promising vaccine candidate.
最广泛的疟原虫物种,间日疟原虫,对公共卫生构成重大威胁。需要一种有效的疫苗来减轻全球疟疾负担。在红细胞阶段疫苗候选物中,间日疟原虫裂殖子表面蛋白 1(PvMSP1)的 19 kDa 片段是最有前途的候选物之一。我们的研究小组之前已经在 PvMSP1 蛋白中定义了几个混杂的 T 辅助表位,这些表位具有能够结合多种 MHC Ⅱ类等位基因的特征。我们在这里描述了一种基于 MSP1 的间日疟原虫重组模块化嵌合体(PvRMC-MSP1),其中包含遗传融合到 PvMSP1 的定义 T 细胞表位。该候选疫苗保留了天然 PvMSP1 的结构元素,并引发了细胞亲嗜性抗体反应以及能够识别 PvMSP1 的 CD4+和 CD8+T 细胞。尽管已经报道了识别血液阶段抗原的 CD8+T 细胞能够控制血液感染,但尚未报道基于 MSP1 的恶性疟原虫或间日疟原虫候选疫苗诱导的 CD8+T 细胞反应。据我们所知,这是首次能够诱导针对 PvMSP1 的 CD8+T 细胞的基于蛋白质的亚单位疫苗。PvRMC-MSP1 蛋白也被来自疟疾流行地区的自然获得抗体所识别,其抗体谱与免受感染有关。这些特征使 PvRMC-MSP1 成为一种有前途的疫苗候选物。