MSP2的抗疟疾疫苗潜能相关性质的分子机制研究

项目名称： MSP2的抗疟疾疫苗潜能相关性质的分子机制研究

项目编号： No.31470775

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 生物科学

项目作者： 张学成

作者单位： 安徽大学

项目金额： 85万元

中文摘要： 疟疾是全球最严重的传染病之一，目前对其的药物治疗因疟原虫渐生的抗药性而受限。通过疫苗预防是另一选择，但很大一部分由于抗原多态性，已有的候选抗疟疾疫苗都只表现出局限的有效性。疟原虫表面抗原MSP2参与疟原虫粘附和入侵红细胞，是很有潜力的抗疟疾疫苗候选。但目前对MSP2功能的理解还很有限，再加上其序列的多样性，使得已开发的MSP2相关疫苗只对部分疟原虫株表现出有限的效力。因此，为提升MSP2作为抗疟疾疫苗的潜能，有必要对其功能和抗原多态性进行深入探究。本项目拟通过核磁共振、透射电镜、荧光、酶联免疫吸附和等温滴定微量热等方法，对各种序列的MSP2全长蛋白和片段的结构、聚集、与膜的相互作用以及抗原性进行研究，以揭示MSP2--特别是其保守区--的功能和抗原多态性的分子机制，为开发效力更高、适用虫株范围更广的基于MSP2的抗疟疾疫苗奠定基础。

中文关键词： 抗疟疾疫苗；蛋白质结构与功能；抗原多态性；分子机制；核磁共振

英文摘要： Malaria is one of the most serious infectious diseases whose treatment is limited by the increasing drug resistance induced in the parasite. Using vaccine to prevent the infection is an alternative strategy to defend malaria. Largely due to antigenic polymorphism, the anti-malaria vaccine candidates so far showed limited efficacy. As malaria surface antigen MSP2 contributes to the parasite attaching to and invading erythrocyte, it is a promising anti-malaria vaccine candidate. However, to date, we know a little about the detail of MSP2 function. In addition, MSP2 sequence is intensly diverse. These make current MSP2-based vaccines only limitedly effective to part of the malaria strains. To enhance the anti-malarial vaccine potential of MSP2, we need understand in depth on the function and the antigenic polymorphism of the protein. In this proposal, we plan to use NMR, TEM, fluorescence, ELISA, ITC, and etc., to investigate the structure, aggregation, membrane interaction and antigenity of full-length and fragment MSP2 of various length and sequence. The results would reveal the molecular mechanism of the function and the antigenic polymorphism of MSP2-especially the conserved regions, and provide theoretical basis for developing the MSP2-based anti-malaria vaccine with higher efficacy and wider applicable scope of malaria strains.

英文关键词： Anti-malaria vaccine;protein structure and function;antigenic polymorphism;molecular mechanism;nuclear magnetic resonance