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The C-terminal region of the Plasmodium yoelii microgamete surface antigen PyMiGS induces potent anti-malarial transmission-blocking immunity in mice.
Vaccine ( IF 5.5 ) Pub Date : 2020-03-05 , DOI: 10.1016/j.vaccine.2020.02.058
Mayumi Tachibana 1 , Minami Baba 1 , Eizo Takashima 2 , Takafumi Tsuboi 2 , Motomi Torii 3 , Tomoko Ishino 1
Affiliation  

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 yoelii microgamete 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.



中文翻译:

约氏疟原虫微配子表面抗原PyMiGS的C末端区域在小鼠中诱导有效的抗疟疾传递阻断免疫。

疟疾传播阻断疫苗(TBV)旨在抑制蚊子中肠内的寄生虫受精或进一步发育。由于接受TBV免疫的个体减少了疟原虫向蚊媒的传播,因此TBV可以作为消除疟疾的一种有前途的策略。我们之前曾报道过一种男性特异性蛋白质PyMiGS(疟原虫yoelii微配子表面蛋白)定位在微配子的表面,并且抗PyMiGS抗体具有很强的传递阻断活性。在这项研究中,我们确定PyMiGS的一个区域,该区域包含诱导有效的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完整)的PyMiGS分为五个重叠区域,命名为I至V,并产生了相应的截短重组蛋白。从抗PyMiGS的全兔抗血清中亲和纯化的抗V区抗体在蚊膜喂养试验中显着减少了卵囊的数量。与通过PyMiGS完全免疫获得的抗体相比,用PyMiGS-V免疫的小鼠产生的抗体识别微配子表面并显示出更高的传递阻断功效。这些结果表明,传递阻断抗体的主要表位在PyMiGS的C末端区域的V区域内。因此,MiGS的V区可能是有希望的受精前TBV候选抗原。

更新日期:2020-03-06
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