疟疾传播阻断疫苗新型候选抗原的确定

项目名称： 疟疾传播阻断疫苗新型候选抗原的确定

项目编号： No.81501769

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 王美莲

作者单位： 中国医科大学

项目金额： 17万元

中文摘要： 传播阻断疫苗对消除疟疾尤其是间日疟具有重要意义，而候选抗原的发掘又是传播阻断疫苗研发的首要环节。本研究利用比较基因组学分析选择了三个在疟原虫有性阶段特异性表达的基因，我们对其中的一个基因进行了系统的研究，证明该基因在疟原虫有性阶段表达，而且其抗血清也证实了具有传播阻断的活性。在此基础之上我们将利用便于遗传分析的鼠疟模型对另外两个传播阻断疫苗候选基因进行功能基因组学分析，通过重组蛋白的表达和小鼠的免疫在体内和体外验证其传播阻断的活性，并利用基因敲除技术揭示该基因在疟原虫有性发育过程中的功能。本研究为今后间日疟传播阻断疫苗的研发提供了非常有力的实验依据。

中文关键词： 疟疾；传播阻断；疫苗；功能基因组学；基因敲除

英文摘要： Transmission blocking vaccine (TBV) plays an essential role in malaria elimination, especially vivax malaria. The discovery of TBV candidates is a prerequisite of TBV development. Through comparative genomics, we have identified three TBV candidates, which are expressed specifically in the sexual stages of the malaria parasites. Systematic analysis of one of the candidates confirmed its specific expression in sexual stages and antisera against this recombinant antigen possessed strong transmission blocking activity. Based on this result, we propose to perform functional genomic studies of the other two candidates by using the genetically more amenable Plasmodium berghei model. By expression of recombinant proteins and immunization of mice, we will obtain antisera for both in vitro and in vivo evaluation of their transmission blocking activities. Further, we will use parasite transfection technology to knock out these candidate genes and study their functions during parasite development. This study will provide guidance to future development of TBVs targeting the Plasmodium vivax malaria.

英文关键词： malaria;transmission blocking;vaccine;functional genomics;genetic knock-out