Integrative Omics of HepB Vaccine Response in Co-Infection with Parasites

总结： 在非洲部分地区，寄生虫病负担很重，包括几种肠道蠕虫， 属，统称为蠕虫和疟疾。最近的一些研究表明这些蠕虫与 特别地，在使免疫应答偏向Th2表型中，导致T细胞的改变， 和B细胞反应。事实上，最近在小鼠中的研究表明，预先存在的感染 曼氏血吸虫下调抗HepB抗体水平并降低对疫苗的应答 多份报告表明，蠕虫感染可能是导致虚弱的原因， 对疫苗的反应。然而，关于以下因素的影响的资料很少： 寄生虫，特别是蠕虫对人体疫苗的宿主免疫应答的影响。 人类疾病和许多生理参数的第二个关键因素是 微生物组肠道微生物组已被证明与广泛的人类疾病相关。 包括许多病毒性和代谢性疾病的疾病。尽管人们逐渐认识到， 微生物组对哺乳动物的免疫和炎症过程具有深远的影响， 微生物组对疫苗应答的影响还不太明确。我们的主要假设是， 感染将通过改变先天免疫的状态来改变HepB疫苗的反应。 系统和微生物组的复杂性，从而定性地损害从头引发 疫苗诱导的T细胞和B细胞免疫。我们的目标是整合和发展免疫 表征宿主对HepB反应的分子和子网络特征的模型 通过使用创新的生物信息学和系统生物学，从低蠕虫负担到高蠕虫负担的疫苗接种 分析。

Summary: In parts of Africa, there is a heavy burden of parasitic diseases, including intestinal worms of several genera, collectively called helminths, and malaria. Some recent studies have implicated the worms in particular, in biasing the immune response towards a Th2 phenotype resulting in alteration of T cell and B cell responses. In fact recent work in mice has shown that pre-existing infection with Schistosoma mansoni down-regulates anti-HepB antibody levels and reduces response to vaccine and multiple reports have indicated that helminthic infections may be a contributing cause for weak responsiveness to the vaccines. However, very little information is available on the influence of parasites in general or helminth in particular on host immune response to vaccines in humans. A second critical contributor to diseases and many physiological parameters in humans is the microbiome. The intestinal microbiome has been shown to be related to a broad range of human diseases including many viral and metabolic diseases. Despite this emerging recognition that the microbiome has profound effects on immune and inflammatory processes in mammals, the effects of the microbiome on vaccine responses are less well defined. Our major hypothesis is that parasitic infection will alter the HepB vaccine response by modifying the state of the innate immune system and microbiome complexity, thereby qualitatively compromising the de novo priming of vaccine-induced T cell and B cell immunity. Our objective is to integrate and develop immune models of the molecular and sub-network signatures that characterize host response to HepB vaccination from low to high helminth burden, by using innovative bioinformatics and systems biology analyses.