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

寄生虫合并感染中乙型肝炎疫苗反应的交互式组学

• 批准号: 10224805
• 负责人: Elias K Haddad
• 金额: $ 23.16万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-10 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10224805
• 关键词: Adjuvant; Adult; Affinity; Animal Model; Anti-Inflammatory Agents; Antibodies; Antibody titer measurement; Antibody-mediated protection; Attenuated; Autoimmune Diseases; B-Lymphocytes; BCG Vaccine; Biodiversity; Cells; Cellular Assay; Cellular Immunity; Child; Chronic; Clinical; Cold Chains; Complement Activation; Ebola; Education; Evolution; Failure; Gene Expression Profiling; HIV/TB; Helminths; Hepatitis B Vaccination; Human; Humoral Immunities; Hypersensitivity; Immune; Immune response; Immune system; Immunity; Immunologics; Impairment; Individual; Infection; Inflammatory; Inflammatory Bowel Diseases; Interferon Type II; Interferons; Interleukin-10; Interleukin-13; Interleukin-5; Kinetics; Link; Memory B-Lymphocyte; Modification; Parasitemia; Parasites; Parasitic infection; Phenotype; Placebos; Predisposition; Process; Production; Proteins; Regulation; Role; Serology; Shapes; Structure; System; T-Lymphocyte; Tetanus Toxoid; Transcriptional Regulation; Transforming Growth Factors; Vaccination; Vaccine Design; Vaccines; Vertebral column; antibody-dependent cellular phagocytosis; antigen binding; co-infection; cytokine; glycosylation; helminth infection; human model; immune function; immunoregulation; improved; influenza virus vaccine; macrophage; mouse model; neutralizing antibody; novel; novel vaccines; pathogen; prevent; response; tool; vaccine effectiveness; vaccine efficacy; vaccine response; vaccine-induced antibodies; vaccine-induced immunity; young adult

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.

项目摘要 尽管我们的临床批准疫苗工具包不断增加，可以挽救数百万人的生命 每年，全球范围内的疫苗有效性并不相同，特别低 发展中国家的覆盖率。疫苗的潜在贡献者之一 发展中国家的失败、可及性、冷链中断和教育已经 被认为是疫苗有效性的结构性障碍。然而，新兴的 人类和动物模型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混杂因素。具体来说，寄生虫感染 超过世界三分之一的地区，并经过数千年的进化，与它们共存 主机。为了实现共存，寄生虫进化出了免疫抑制策略 极大地改变宿主的免疫系统。这些改变包括增强 抗炎细胞因子表达谱和倾斜的 T 辅助细胞 (Th) 免疫 共同涉及对新发感染和新感染的反应受损 疫苗接种。然而，寄生虫感染对抗体免疫改变的影响已经 更具争议性，寄生虫感染与总体减少有关 某些疫苗中存在抗体滴度，而另一些则不然。然而，鉴于 Th 的关键作用 免疫在编程体液反应中，虽然寄生是合理的 感染可能只会不同程度地改变体液免疫反应的总体程度， 这些免疫学变化可能对塑造免疫质量产生巨大影响 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两种状态的影响 疫苗诱导记忆 B 细胞反应以及记忆 B 细胞的功能特征 疫苗诱导抗体。