The C-terminal region of the Plasmodium yoelii microgamete surface antigen PyMiGS induces potent anti-malarial transmission-blocking immunity in mice
The C-terminal region of the Plasmodium yoelii microgamete surface antigen PyMiGS induces potent anti-malarial transmission-blocking immunity in mice
复制标题
约氏疟原虫小配子表面抗原 PyMiGS 的 C 末端区域在小鼠中诱导有效的抗疟疾传播阻断免疫
DOI：
10.1016/j.vaccine.2020.02.058
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发表时间：
2020
期刊：
影响因子：
5.5
通讯作者：
Ishino Tomoko
中科院分区：
文献类型：
--
作者：
Tachibana Mayumi;Baba Minami;Takashima Eizo;Tsuboi Takafumi;Torii Motomi;Ishino Tomoko
疟疾传播阻断疫苗（TBVs）旨在抑制寄生虫在蚊子中肠内受精或进一步发育。由于tbv免疫个体减少了疟疾寄生虫向蚊虫媒介的传播，tbv可能成为消除疟疾的一种有希望的策略。我们之前报道过一种男性特异性蛋白PyMiGS（约利亚微配子表面蛋白）定位于小配子表面，抗PyMiGS抗体具有很强的传递阻断活性。在这项研究中，我们确定了PyMiGS的一个区域，该区域含有诱导强效传输阻断抗体的表位。将不包括n端信号序列和c端疏水区（PyMiGS-full）的PyMiGS分成5个重叠区域，命名为I到V，并产生相应的截断重组蛋白。从抗pymigs -full兔抗血清中亲和纯化的抗V区抗体，在蚊子膜采食实验中显著减少卵囊数量。PyMiGS-V免疫小鼠产生的抗体识别小配子表面，并表现出比PyMiGS-V全免疫获得的抗体更高的传播阻断效力。这些结果表明，传递阻断抗体的主要表位位于PyMiGS c -末端的V区。因此，MiGS的V区可能是一种很有前景的受精前TBV候选抗原。
Malaria transmission-blocking vaccines (TBVs) aim to inhibit parasite fertilization or further development within the mosquito midgut. Because TBV-immunized individuals reduce the transmission of malaria parasites to mosquito vectors, TBVs could serve as a promising strategy to eliminate malaria. We previously reported that a male specific protein, PyMiGS (Plasmodium yoeliimicrogamete surface protein), is localized to the surface of microgametes and anti-PyMiGS antibodies have strong transmission-blocking activity. In this study we determine a region of PyMiGS that contains epitopes inducing potent transmission-blocking antibodies. PyMiGS excluding the N-terminal signal sequence and C-terminal hydrophobic region (PyMiGS-full) was divided into five overlapping regions, named I through V, and corresponding truncated recombinant proteins were produced. Anti-region V antibody, affinity-purified from anti-PyMiGS-full rabbit antiserum, significantly reduced the number of oocysts in a mosquito membrane-feeding assay. Antibodies from mice immunized with PyMiGS-V recognized the microgamete surface and showed higher transmission-blocking efficacy than antibodies obtained by PyMiGS-full immunization. These results indicate that the major epitopes for transmission-blocking antibodies are within region V at the C-terminal region of PyMiGS. Therefore, region V of MiGS could be a promising pre-fertilization TBV candidate antigen.