Identifying the common biological properties of parasite vaccine targets

由于影响牲畜健康的传染病，非洲数百万人的生计受到威胁，而牲畜为他们提供基本的食物、牛奶、衣服和牵引力。一种主要的牲畜疾病是动物非洲锥虫病，每年造成超过10亿美元的生产力损失。这一疾病的影响如此之大，以至于联合国认为它是“非洲消除贫困斗争的核心”。我们已经建立了两种引起AAT的寄生虫的感染模型：T。congolense和T.间日疟原虫，并使用重组蛋白文库，已经鉴定了可以赋予无菌保护的亚单位疫苗候选物（参见Auteman等人，Nature 2021 v595 p96 PMID：34040257）。我们希望利用这些发现来确定成功的候选疫苗的生物学特性的共同点，最终目的是提高疫苗效力，并采取更合理的方法来选择其他寄生虫病的靶点。该项目将涉及最新的质谱技术，以确定寄生虫细胞表面蛋白的细胞表面停留时间。研究结果将用于改进疫苗设计，这些疫苗将在动物模型中进行测试，并揭示这些临床和经济上重要的寄生虫生物学的基本方面。

The livelihoods of millions of people living in Africa are at risk due to infectious diseases that affect the health of livestock animals that provide them with essential food, milk, clothing and draught power. One major livestock disease is animal African trypanosomiasis (AAT) which causes annual productivity losses of over $1 billion. Such is the impact of this disease that the United Nations consider it to "lie at the heart of Africa's struggle against poverty". We have established infection models of both AAT-causing parasites: T. congolense and T. vivax, and using a library of recombinant proteins have identified subunit vaccine candidates that can confer sterile protection (see Autheman et al. Nature 2021 v595 p96 PMID:34040257). We would like to use these findings to identify commonalities in the biological properties of successful vaccine candidates with the ultimate aim of improving vaccine efficacy and taking a more rational approach to selecting targets for other parasitic diseases. The project will involve the latest in mass spectrometry techniques to establish cell surface residency times of parasite cell surface proteins. The results will be used to improve vaccine design which will be tested in animal models and also reveal fundamental aspects of the biology of these clinically and economically important parasites.