Immunization with mosquito AgTRIO protein to prevent malaria

使用蚊子 AgTRIO 蛋白进行免疫预防疟疾

基本信息

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
项目类别：
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

项目摘要

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上主要的公共卫生威胁之一。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)。目前尚未研制出高效、安全且经 FDA 批准的人类疟疾疫苗开发出最成熟的候选疟疾疫苗 RTS,S/AS01，这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会随着时间的推移而减弱（1-10）。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，我们在其中生产了重组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这项工作表明，可以针对蚊子唾液中的蛋白质来预防。疟原虫感染。该提案的目的是制定 AgTRIO 主动免疫策略我们的长期目标是开发一种疫苗。这将为人类提供强有力的疟疾保护。