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

项目摘要 尽管我们越来越多的临床批准的疫苗工具包，防止数百万人的生命 每年，疫苗的有效性在地球仪上并不相等， 发展中国家的覆盖率。在疫苗的潜在贡献者中， 发展中国家的失败，可访问性，冷链断裂和教育 被认为是疫苗有效性的结构性障碍。但新兴 人类和动物模型的证据都指出寄生虫感染的关键作用 作为疫苗诱导免疫的免疫学混杂因素。具体来说，寄生虫感染 超过三分之一的世界，并已演变了数千年，以共存， hosts.为了实现共存，寄生虫已经进化出免疫抑制策略 能极大地改变宿主的免疫系统这些变化包括增强 抗炎细胞因子表达谱和倾斜的辅助性T细胞（Th）免疫， 共同参与了对新发感染和 预防针然而，寄生虫感染对抗体免疫改变的影响， 更有争议的是，寄生虫感染与整体减少有关， 某些疫苗中的抗体滴度，但其他疫苗中没有。然而，考虑到Th的关键作用， 免疫在编程体液反应，这是合理的，虽然寄生 感染可能仅改变体液免疫应答的总体大小， 这些免疫学变化可能会对塑造 体液免疫反应。因此，在这个项目下，我们的目标是全面 剖析寄生虫合并感染对改变和塑造两种状态的影响， 疫苗诱导的记忆B细胞应答以及免疫抑制剂的功能特征。 疫苗诱导的抗体。

Project Abstract Despite our growing tool kit of clinically approved vaccines that prevent millions of lives annually, vaccine effectiveness is not equivalent across the globe, with particularly low coverage rates in the developing world. Among the potential contributors to vaccine failures in the developing world, accessibility, cold chain breaks, and education have been implicated as structural barriers to vaccine effectiveness. However, emerging evidence both in humans and animal models point to a critical role of parasitic infections as immunological confounders of vaccine induced immunity. Specifically, parasites infect more than a third of the world and have evolved over millennia to co-exist with their hosts. To achieve co-existence, parasites have evolved immunosuppressive strategies that dramatically alter the host’s immune system. These alterations include enhanced anti-inflammatory cytokine expression profiles and skewed T-helper (Th) immunity that collectively have been implicated in impaired response to both de novo infections and vaccination. However, the impact of parasitic infections on altered antibody immunity has been more controversial, where parasitic infection has been linked to reduced overall antibody titers in some vaccines but not others. However, given the critical role of Th immunity in programming the humoral response, it is plausible that while parasitic infection may only alter the overall magnitude of the humoral immune response variably, that these immunologic changes may have a dramatic impact on shaping the quality of the humoral immune response. Thus under this project we aim to comprehensively dissect the impact of parasitic co-infection on altering and shaping both the state of the vaccine induced memory B cell response as well as the functional character of the vaccine induced antibodies.