Laboratory of Pathogen Infection and Immunity, Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, People's Republic of China.
Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
Infect Immun. 2021 Jan 19;89(2). doi: 10.1128/IAI.00645-20.
Research on erythrocytic merozoite antigens is critical for identifying potential vaccine candidates in reducing disease. However, many studies are constrained by its inability to undergo long-term culture Conserved across all spp., merozoite surface proteins are essential for invasion into erythrocytes and highly expressed on erythrocytic merozoites, thus making it an ideal vaccine candidate. In clinical trials, the merozoite surface protein 1 (PvMSP1-19) vaccine candidate alone has shown to have limited immunogenicity in patients; hence, we incorporate the highly conserved and immunogenic C terminus of both merozoite surface protein 8 (PvMSP8) and PvMSP1-19 to develop a multicomponent chimeric protein rPvMSP8+1 for immunization of mice. The resulted chimeric rPvMSP8+1 antibody was shown to recognize native protein MSP8 and MSP1-19 of mature schizonts. In the immunized mice, an elevated antibody response was observed in the rPvMSP8+1-immunized group compared to that immunized with single-antigen components. In addition, we examined the growth inhibition of these antibodies against (Berok strain) parasites, which is phylogenetically close to and sustains long-term culture Similarly, the chimeric anti-rPvMSP8+1 antibodies recognize MSP8 and MSP1-19 on mature schizonts and showed strong inhibition via growth inhibition assay. This study provides support for a new multiantigen-based paradigm rPvMSP8+1 to explore potential chimeric vaccine candidates against malaria using sister species .
红细胞裂殖子抗原的研究对于确定潜在的疫苗候选物以减少疾病至关重要。然而,许多研究受到其无法进行长期培养的限制。
裂殖子表面蛋白在所有 spp.中都保守,对于侵入红细胞至关重要,并且在红细胞裂殖子上高度表达,因此成为理想的疫苗候选物。在临床试验中,单独的裂殖子表面蛋白 1 (PvMSP1-19)疫苗候选物已显示出对患者的免疫原性有限;因此,我们将高度保守和免疫原性的裂殖子表面蛋白 8 (PvMSP8)和 PvMSP1-19 的 C 末端结合起来,开发一种多成分嵌合蛋白 rPvMSP8+1 用于免疫小鼠。结果表明,嵌合 rPvMSP8+1 抗体能够识别成熟裂殖体中的天然蛋白 MSP8 和 MSP1-19。在免疫小鼠中,与单抗原成分免疫相比,rPvMSP8+1 免疫组观察到抗体反应升高。此外,我们检查了这些抗体对 (Berok 株)寄生虫的生长抑制作用,该寄生虫与 密切相关,并能长期维持培养。同样,嵌合抗-rPvMSP8+1 抗体识别成熟裂殖体中的 MSP8 和 MSP1-19,并通过生长抑制试验显示出强烈的抑制作用。这项研究为使用姐妹种探索针对 疟疾的新型多抗原基 rPvMSP8+1 提供了支持,以寻找潜在的嵌合疫苗候选物。