Immunization with mosquito AgTRIO protein to prevent malaria

项目摘要 疟疾是世界上主要的公共卫生威胁之一。这种疾病是通过 当一只受感染的雌性按蚊在寻找吸血食物时， 与疟原虫子孢子一起进入脊椎动物宿主的皮肤（1，2）。迄今为止， 高效、安全和FDA批准的抗疟疾的人用疫苗还没有被 开发最成熟的疟疾候选疫苗RTS，S/AS 01，是一种 基于恶性疟原虫环子孢子蛋白的重组蛋白，赋予 对疟疾的适度保护，随着时间的推移而减弱（1-10）。非常需要一个 改进的疟疾疫苗，这就是这项提案的目标-使用蛋白质， 影响疟原虫子孢子感染脊椎动物能力的蚊子唾液 主持人 在我们最近发表的研究（11）中，我们在女性的唾液中发现了一种蛋白质， 冈比亚按蚊，名为AgTRIO。我们在大肠杆菌中生产了重组AgTRIO， 大肠杆菌，并证明了用重组AgTRIO主动免疫小鼠 显著减少蚊媒伯氏疟原虫和恶性疟原虫感染 动物们。这项工作表明，蚊子唾液中的一种蛋白质可以有针对性地预防 疟原虫感染。 该提案的目的是制定一项使用AgTRIO进行主动免疫的战略 在真核表达系统中产生的蛋白质。我们的长期目标是研制一种疫苗 这将为人类提供强大的抗疟疾保护。

PROJECT SUMMARY Malaria is one of the world’s major public health threats. The disease is transmitted when an infected female Anopheles mosquito, while probing for a blood meal, injects saliva together with Plasmodium sporozoites into the skin of the vertebrate host (1, 2). To date, a highly effective, safe and FDA-approved human vaccine against malaria has not been developed. The most established malaria vaccine candidate, RTS,S/AS01, which is a recombinant protein based on the circumsporozoite protein of Plasmodium falciparum, confers moderate protection against malaria which wanes over time (1-10). There is great need for an improved vaccine against malaria, and that is the goal of this proposal - using a protein in mosquito saliva that influences the ability of Plasmodium sporozoites to infect the vertebrate host. In our recently published study (11), we identified a protein in the saliva of female Anopheles gambiae mosquitoes, named AgTRIO. We produced recombinant AgTRIO in Escherichia coli and demonstrated that active immunization of mice with recombinant AgTRIO significantly reduced mosquito-borne Plasmodium berghei and Plasmodium falciparum infection of the animals. This work showed that a protein in mosquito saliva can be targeted to prevent Plasmodium infection. The aim of this proposal is to develop a strategy for active immunization with AgTRIO protein produced in a eukaryotic expression system. Our long-term goal is to develop a vaccine that will provide robust protection against malaria for use in humans.