Characterization of PSOP26 as an ookinete surface antigen with improved transmission-blocking activity when fused with PSOP25.

Characterization of PSOP26 as an ookinete surface antigen with improved transmission-blocking activity when fused with PSOP25.
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PSOP26 作为动动表面抗原的表征,与 PSOP25 融合时具有改善的传输阻断活性

DOI:
10.1186/s13071-022-05294-8
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发表时间:
2022-05-23
影响因子:
3.2
通讯作者:
--
中科院分区:
医学2区
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疟原虫合子到动合子的发育转变是在蚊子载体中建立感染的重要步骤,并且在此阶段表达的抗原是传播阻断疫苗(TBV)的潜在靶点。分泌型动合子蛋白26(PSOP 26)是一种新发现的动合子表面蛋白。抗PSOP 26血清具有中等的传播阻断活性,表明进一步研究这种蛋白作为TBV靶点的益处。通过靶向基因破坏分析psop 26的功能。在大肠杆菌系统中表达嵌合PSOP 25-PSOP 26蛋白。将PSOP 25-PSOP 26融合蛋白与混合蛋白(PSOP 25 + PSOP 26)或单一蛋白(PSOP 26或PSOP 25)一起沿着用于免疫小鼠。采用酶联免疫吸附试验(ELISA)、间接免疫荧光试验(IFA)和Western blot分析血清抗体效价和免疫原性。使用体外和体内试验评估来自不同免疫方案的血清的传播阻断活性。PSOP 26是疟原虫配子和动合子中表达的表面蛋白。该蛋白质是无性血液阶段发育,配子发生和合子形成所必需的,但对于合子到动合子的发育过渡是必需的。具体而言,在喂食psop 26无效突变体的蚊子中,感染的患病率和卵囊密度均降低。单个PSOP 25和PSOP 26片段的混合物(PSOP 25 + PSOP 26)以及嵌合体(PSOP 25-PSOP 26)在小鼠中引起高抗体水平,无免疫学干扰。针对混合和融合蛋白的抗血清引起比针对单一PSOP 26抗原的抗血清更高的传播减少活性(TRA),但与单独针对PSOP 25抗原的抗血清相当。PSOP 26在合子向动合子的发育转变中起关键作用。PSOP 25是一种有前途的TBV候选物,可以单独用于靶向动合子阶段。在线版本包含补充材料,可通过10.1186/s13071-022-05294-8获得。
The Plasmodium zygote-to-ookinete developmental transition is an essential step for establishing an infection in the mosquito vector, and antigens expressed during this stage are potential targets for transmission-blocking vaccines (TBVs). The secreted ookinete protein 26 (PSOP26) is a newly identified ookinete surface protein. The anti-PSOP26 serum has moderate transmission-blocking activity, indicating the benefit of further investigating this protein as a target for TBVs. The function of psop26 was analyzed by targeted gene disruption. A chimeric PSOP25-PSOP26 protein was expressed in the Escherichia coli system. The PSOP25-PSOP26 fusion protein, along with mixed (PSOP25 + PSOP26) or single proteins (PSOP26 or PSOP25), were used for the immunization of mice. The antibody titers and immunogenicity of individual sera were analyzed by enzyme-linked immunoassay (ELISA), indirect immunofluorescence assay (IFA), and Western blot. The transmission-blocking activity of sera from different immunization schemes was assessed using in vitro and in vivo assays. PSOP26 is a surface protein expressed in Plasmodium gametes and ookinetes. The protein is dispensable for asexual blood-stage development, gametogenesis, and zygote formation, but is essential for the zygote-to-ookinete developmental transition. Specifically, both the prevalence of infections and oocyst densities were decreased in mosquitoes fed on psop26-null mutants. Mixtures of individual PSOP25 and PSOP26 fragments (PSOP25 + PSOP26), as well as chimeras (PSOP25-PSOP26), elicited high antibody levels in mice, with no immunological interference. Antisera against the mixed and fusion proteins elicited higher transmission-reducing activity (TRA) than antisera against the single PSOP26 antigen, but comparable to antisera against PSOP25 antigen alone. PSOP26 plays a critical role in the zygote-to-ookinete developmental transition. PSOP25 is a promising TBV candidate that could be used alone to target the ookinete stage. The online version contains supplementary material available at 10.1186/s13071-022-05294-8.
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发表时间: 2012-09
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影响因子: 6.7
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