The Plasmodium berghei sexual stage antigen PSOP12 induces anti-malarial transmission blocking immunity both in vivo and in vitro
The Plasmodium berghei sexual stage antigen PSOP12 induces anti-malarial transmission blocking immunity both in vivo and in vitro
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DOI：
10.1016/j.vaccine.2014.11.038
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发表时间：
2015-01-09
期刊：
影响因子：
5.5
通讯作者：
Blagborough, A. M.
中科院分区：
文献类型：
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作者：
Sala, K. A.;Nishiura, H.;Blagborough, A. M.
抗疟疾传播阻断疫苗(TBV)旨在通过针对疟原虫的有性/运动阶段来抑制疟疾从人到蚊子的传播。这种干预措施的成功使用将随后减少人类人口中的疟疾感染病例，从而导致当地消除疟疾。目前只有五名首席TBV考生在考试中。因此，有必要确定新的抗原，以允许新的有效的TBV的形成。在这里，我们描述了基于杆状病毒双表达系统(BDES)的针对伯氏疟原虫PSOP12的潜在的TBV(BDES-PbPSOP12)的设计和评价，使抗原能够在病毒颗粒表面和受感染的哺乳动物细胞内表达。研究表明，PSOP12(可能的分泌型动子蛋白12)在寄生虫的有性阶段(配子细胞、配子和动子)中表达，是6-半胱氨酸原虫蛋白家族的成员。我们证明PSOP12在寄生虫的有性/运动形式中表达，并且从BDes-PbPSOP12免疫的小鼠获得的血清可以识别寄生虫的雄配子和雌性配子的表面，以及寄生虫的运动阶段。用BDES-PbPSOP12免疫小鼠，通过主动免疫在体内赋予了适度但显著的传播阻断活性(卵囊强度降低了53.1%，卵囊患病率降低了10.9%)。对体外传播阻断效力的进一步评估显示出剂量依赖的反应，强度降低高达76.4%，流行率降低47.2%。我们的数据表明，PSOP12在疟原虫spp.可能是一个潜在的新的TBV目标候选，进一步的实验来检测人类疟疾寄生虫中的蛋白质将是合乎逻辑的。(C)2014年提交人。爱思唯尔有限公司出版。
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.