The Plasmodium falciparum Cell-Traversal Protein for Ookinetes and Sporozoites as a Candidate for Preerythrocytic and Transmission-Blocking Vaccines.
The Plasmodium falciparum Cell-Traversal Protein for Ookinetes and Sporozoites as a Candidate for Preerythrocytic and Transmission-Blocking Vaccines.
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恶性疟原虫细胞 - 转化蛋白用于卵巢和子孢子作为候选次细胞和传播封锁疫苗的候选者。
DOI：
10.1128/iai.00498-16
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发表时间：
2017-02
影响因子：
3.1
通讯作者：
Gutierrez GM
中科院分区：
文献类型：
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作者：
Espinosa DA;Vega-Rodriguez J;Flores-Garcia Y;Noe AR;Muñoz C;Coleman R;Bruck T;Haney K;Stevens A;Retallack D;Allen J;Vedvick TS;Fox CB;Reed SG;Howard RF;Salman AM;Janse CJ;Khan SM;Zavala F;Gutierrez GM
最近的研究表明，针对疟原虫动合子和子孢子的细胞穿越蛋白（CelTOS）的免疫应答可以抑制寄生虫感染。虽然这些研究为靶向这种蛋白质的疫苗的开发提供了重要的证据，但这些反应是否可以在体内参与恶性疟原虫CelTOS仍然是未知的。使用新开发的表达恶性疟原虫CelTOS（PfCelTOS）的啮齿类疟疾嵌合寄生虫，我们评估了由疫苗接种引起的体内免疫应答的保护作用，并评估了特异性针对PfCelTOS的单克隆抗体的中和能力。用重组恶性疟原虫CelTOS与吡喃葡萄糖基脂质澄清剂-稳定乳剂（GLA-SE）或吡喃葡萄糖基脂质澄清剂-脂质体-QS 21（GLA-LSQ）佐剂系统组合免疫的小鼠显著抑制子孢子肝细胞感染。值得注意的是，针对PfCelTOS的单克隆抗体强烈抑制冈比亚按蚊中表达PfCelTOS的恶性疟原虫和伯氏疟原虫的卵囊发育。综上所述，我们的结果表明，疫苗接种或被动免疫引起的抗CelTOS反应可以抑制子孢子和动合子感染，并损害载体传播。
Recent studies have shown that immune responses against the cell-traversal protein for Plasmodium ookinetes and sporozoites (CelTOS) can inhibit parasite infection. While these studies provide important evidence toward the development of vaccines targeting this protein, it remains unknown whether these responses could engage the Plasmodium falciparum CelTOS in vivo. Using a newly developed rodent malaria chimeric parasite expressing the P. falciparum CelTOS (PfCelTOS), we evaluated the protective effect of in vivo immune responses elicited by vaccination and assessed the neutralizing capacity of monoclonal antibodies specific against PfCelTOS. Mice immunized with recombinant P. falciparum CelTOS in combination with the glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE) or glucopyranosyl lipid adjuvant-liposome-QS21 (GLA-LSQ) adjuvant system significantly inhibited sporozoite hepatocyte infection. Notably, monoclonal antibodies against PfCelTOS strongly inhibited oocyst development of P. falciparum and Plasmodium berghei expressing PfCelTOS in Anopheles gambiae mosquitoes. Taken together, our results demonstrate that anti-CelTOS responses elicited by vaccination or passive immunization can inhibit sporozoite and ookinete infection and impair vector transmission.