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

项目摘要 尽管我们的临床批准疫苗工具包越来越多，可以预防数百万人的生命 每年，疫苗在全球的有效性并不相同，尤其是低 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、可获得性、冷链断裂和教育 被认为是疫苗有效性的结构性障碍。然而，新兴的 在人类和动物模型中的证据都表明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子。具体地说，寄生虫感染 世界上超过三分之一的地区，经过数千年的进化，与他们的 主持人。为了实现共存，寄生虫进化出了免疫抑制策略 这极大地改变了宿主的免疫系统。这些更改包括增强版 抗炎细胞因子表达谱和扭曲的T辅助细胞(Th)免疫 共同牵涉到对新感染和新感染的反应受损 接种疫苗。然而，寄生虫感染对改变的抗体免疫的影响 更具争议性，寄生虫感染与总体减少有关 有些疫苗可以检测抗体效价，但其他疫苗则不能。然而，鉴于Th的关键作用 免疫编程的体液反应，这是看似合理的，虽然寄生 感染可能只会可变地改变体液免疫反应的总体大小， 这些免疫变化可能会对塑造人类免疫系统的质量产生巨大影响 体液免疫反应。因此，在这个项目下，我们的目标是全面 剖析寄生虫混合感染对改变和塑造人类免疫功能状态的影响 疫苗诱导的记忆B细胞反应及其功能特征 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.