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首页> 外文期刊>Vaccine >The Plasmodium berghei sexual stage antigen PSOP12 induces anti-malarial transmission blocking immunity both in vivo and in vitro
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The Plasmodium berghei sexual stage antigen PSOP12 induces anti-malarial transmission blocking immunity both in vivo and in vitro

机译：伯氏疟原虫性阶段抗原PSOP12在体内和体外均诱导抗疟疾传播阻断免疫

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Anti-malarial transmission-blocking vaccines (TBVs) aim to inhibit the transmission of Plasmodium from humans to mosquitoes by targeting the sexual/ookinete stages of the parasite. Successful use of such interventions will subsequently result in reduced cases of malarial infection within a human population, leading to local elimination. There are currently only five lead TBV candidates under examination. There is a consequent need to identify novel antigens to allow the formulation of new potent TBVs. Here we describe the design and evaluation of a potential TBV (BDES-PbPSOP12) targeting Plasmodium berghei PSOP12 based on the baculovirus dual expression system (BDES), enabling expression of antigens on the surface of viral particles and within infected mammalian cells. In silico studies have previously suggested that PSOP12 (Putative Secreted Ookinete Protein 12) is expressed within the sexual stages of the parasite (gametocytes, gametes and ookinetes), and is a member of the previously characterized 6-Cys family of plasmodial proteins. We demonstrate that PSOP12 is expressed within the sexual/ookinete forms of the parasite, and that sera obtained from mice immunized with BDES-PbPSOP12 can recognize the surface of the male and female gametes, and the ookinete stages of the parasite. Immunization of mice with BDES-PbPSOP12 confers modest but significant transmission-blocking activity in vivo by active immunization (53.1% reduction in oocyst intensity, 10.9% reduction in oocyst prevalence). Further assessment of transmission-blocking potency ex vivo shows a dose-dependent response, with up to a 76.4% reduction in intensity and a 47.2% reduction in prevalence observed. Our data indicates that PSOP12 in Plasmodium spp. could be a potential new TBV target candidate, and that further experimentation to examine the protein within human malaria parasites would be logical. (C) 2014 The Authors. Published by Elsevier Ltd.
机译：抗疟疾传播阻断疫苗（TBV）旨在通过针对寄生虫的性/速动阶段来抑制疟原虫从人到蚊子的传播。成功地使用这些干预措施将导致减少人群中的疟疾感染病例，从而导致局部消除。目前，只有五名领先的TBV候选人正在接受检查。因此，需要鉴定新的抗原以允许配制新的有效TBV。在这里，我们描述了基于杆状病毒双重表达系统（BDES）的针对伯氏疟原虫PSOP12的潜在TBV（BDES-PbPSOP12）的设计和评估，使抗原能够在病毒颗粒表面和感染的哺乳动物细胞内表达。在计算机上的研究以前表明，PSOP12（推测的分泌型卵母细胞蛋白12）在寄生虫的有性阶段（配子细胞，配子和卵子）内表达，并且是以前表征的纤溶酶6-Cys家族成员。我们证明PSOP12在寄生虫的有性/纯合子形式中表达，并且从用BDES-PbPSOP12免疫的小鼠获得的血清可以识别雄性和雌性配子的表面以及寄生虫的同化子阶段。用BDES-PbPSOP12免疫小鼠可通过主动免疫在体内产生适度但明显的传播阻断活性（卵囊强度降低53.1％，卵囊患病率降低10.9％）。进一步评估离体传输阻滞能力显示出剂量依赖性反应，观察到强度降低了76.4％，患病率降低了47.2％。我们的数据表明，疟原虫属物种中存在PSOP12。可能是潜在的新的TBV靶标候选物，并且进行进一步实验以检测人疟疾寄生虫中的蛋白质将是合乎逻辑的。 （C）2014作者。由Elsevier Ltd.发布

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