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

摘要： 在非洲部分地区，有沉重的寄生虫病负担，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 特别是在使免疫反应偏向Th2表型导致T细胞改变方面 和B细胞反应。事实上，最近在老鼠身上的研究表明，先前存在的感染 曼氏血吸虫下调抗-HBs抗体水平并降低对疫苗的反应 多份报告表明，寄生虫感染可能是导致虚弱的原因之一。 对疫苗的反应性。然而，关于艾滋病的影响的信息很少。 一般情况下，寄生虫或蠕虫对宿主对疫苗的免疫反应有影响。 导致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，包括许多病毒性和代谢性疾病。尽管这一新出现的认识到 微生物组对哺乳动物的免疫和炎症过程有深远的影响， 关于疫苗反应的微生物组还没有很好的定义。我们的主要假设是寄生虫 感染会通过改变先天免疫状态来改变乙肝疫苗的反应 系统和微生物组的复杂性，从而定性地影响从头开始 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 表征宿主对乙肝病毒应答的分子和子网络特征的模型 利用创新的生物信息学和系统生物学，从低到高的蠕虫负担进行疫苗接种 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.