Identifying the common biological properties of parasite vaccine targets

由于传染病影响牲畜的健康，生活在非洲的数百万人的生计受到威胁，这些牲畜为他们提供了基本的食物、牛奶、衣服和动力。一种主要的牲畜疾病是动物非洲锥虫病（AAT），每年造成的生产力损失超过10亿美元。这一疾病的影响如此之大，联合国认为它“处于非洲反贫困斗争的核心”。我们已经建立了两种引起aat的寄生虫的感染模型：刚果体和间日疟原虫，并利用重组蛋白文库确定了可以提供无菌保护的亚单位候选疫苗（见Autheman等）。Nature 2021 v595 p96 pid:34040257)。我们希望利用这些发现来确定成功候选疫苗生物学特性的共性，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，以建立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.