FREP1蛋白的纤维蛋白原样结构域是一种广谱的疟疾传播阻断疫苗抗原。
The fibrinogen-like domain of FREP1 protein is a broad-spectrum malaria transmission-blocking vaccine antigen.
作者信息
Niu Guodong, Franc A Caio, Zhang Genwei, Roobsoong Wanlapa, Nguitragool Wang, Wang Xiaohong, Prachumsri Jetsumon, Butler Noah S, Li Jun
机构信息
Department of Biological Sciences, Florida International University, Miami, Florida 33199.
Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019.
出版信息
J Biol Chem. 2017 Jul 14;292(28):11960-11969. doi: 10.1074/jbc.M116.773564. Epub 2017 May 22.
FREP1 in mosquito midguts facilitates parasite transmission. The fibrinogen-like (FBG) domain of FREP1 is highly conserved (>90% identical) among species from different continents, suggesting that anti-FBG antibodies may block malaria transmission to all anopheline mosquitoes. Using standard membrane-feeding assays, anti-FREP1 polyclonal antibodies significantly blocked transmission of and to and , respectively. Furthermore, studies of mice immunized with FBG achieved >75% blocking efficacy of to without triggering immunopathology. Anti-FBG serum also reduced >81% of infection to Finally, we showed that FBG interacts with gametocytes and ookinetes, revealing the molecular mechanism of its antibody transmission-blocking activity. Collectively, our data support that FREP1-mediated transmission to mosquitoes is a conserved pathway and that targeting the FBG domain of FREP1 will limit the transmission of multiple species to multiple species.
蚊子中肠中的FREP1促进寄生虫传播。FREP1的纤维蛋白原样（FBG）结构域在来自不同大陆的物种中高度保守（>90%相同），这表明抗FBG抗体可能会阻断疟疾向所有按蚊的传播。使用标准的膜饲法，抗FREP1多克隆抗体分别显著阻断了疟原虫向斯氏按蚊和冈比亚按蚊的传播。此外，用FBG免疫小鼠的研究实现了对伯氏疟原虫>75%的阻断效果，且未引发免疫病理学。抗FBG血清也将约氏疟原虫感染斯氏按蚊的比例降低了>81%。最后，我们表明FBG与疟原虫配子体和动合子相互作用，揭示了其抗体传播阻断活性的分子机制。总体而言，我们的数据支持FREP1介导的疟原虫向蚊子的传播是一条保守途径，并且靶向FREP1的FBG结构域将限制多种疟原虫物种向多种按蚊物种的传播。
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