Immunization with mosquito AgTRIO protein to prevent malaria

使用蚊子 AgTRIO 蛋白进行免疫预防疟疾

• 批准号: 9916709
• 负责人: Erol Fikrig
• 金额: $ 29.34万
• 依托单位: L2 DIAGNOSTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-16 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9916709
• 关键词: Achievement; Active Immunization; Adjuvant; Aluminum Hydroxide; Animals; Anopheles Genus; Anopheles gambiae; Baculoviruses; Blood; Cells; Clinical; Culicidae; Disease; Dose; Escherichia coli; Exposure to; FDA approved; Female; Formulation; Goals; Hour; Human; Immune response; Immunization; Immunize; Infection; Insecta; Liver; MF59; Malaria; Malaria Vaccines; Measures; Mus; Names; Parasitemia; Phase; Plasmodium; Plasmodium berghei; Plasmodium falciparum; Proteins; Public Health; Publications; Publishing; Quantitative Reverse Transcriptase PCR; Recombinant Proteins; Recombinants; Regimen; Saliva; Skin; Sporozoites; System; Time; Vaccinated; Vaccine Antigen; Vaccine Design; Work; base; circumsporozoite protein; efficacy testing; human pathogen; humanized mouse; improved; mosquito-borne; nonhuman primate; pathogen; phase 2 study; prevent; protective effect; response; vaccine candidate; vaccine development

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.

项目概要 疟疾是世界主要的公共卫生威胁之一。该病已传播 当一只受感染的雌性按蚊在探寻血粉时注射唾液 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，一个 目前尚未研制出高效、安全且经 FDA 批准的人类疟疾疫苗 发达。最成熟的候选疟疾疫苗 RTS,S/AS01 基于恶性疟原虫环子孢子蛋白的重组蛋白，赋予 对疟疾的适度保护会随着时间的推移而减弱 (1-10)。非常需要一个 改进抗疟疾疫苗，这就是该提案的目标 - 使用蛋白质 蚊子唾液影响疟原虫子孢子感染脊椎动物的能力 主持人。 在我们最近发表的研究 (11) 中，我们在女性唾液中发现了一种蛋白质 冈比亚按蚊，命名为AgTRIO。我们生产重组 AgTRIO 大肠杆菌并证明重组AgTRIO对小鼠主动免疫 显着减少蚊媒伯氏疟原虫和恶性疟原虫感染 的动物。这项工作表明，蚊子唾液中的一种蛋白质可以针对性地预防 疟原虫感染。 该提案的目的是制定 AgTRIO 主动免疫策略 真核表达系统中产生的蛋白质。我们的长期目标是开发疫苗 这将为人类提供强有力的疟疾保护。