Integrating innate and adaptive pathways in vaccine responses

描述(由申请人提供)：该计划的目标是对人类持久的保护性免疫反应的进化进行定向调查，以便更好地了解有效疫苗和佐剂的要求。提交此申请是为了获得洛克菲勒大学人类免疫学合作中心的资金。我们的计划是高度集成的，基于个人投资机构之间关于定义人类免疫学基本原则的长期、富有成效的合作，利用洛克菲勒大学医院、赞维尔·科恩疫苗中心和洛克菲勒大学临床和翻译科学奖(CTSA)的基础设施。拟议的研究项目被设计为假设检验、机制研究，在接种传染病疫苗的背景下审查人类免疫反应的激活和调节的新方面。参与调查的人员是识别 研究人类免疫应答的基本机制，有助于树突状细胞的初步鉴定、抗体效应器功能的多样性和Fc受体作为免疫介体的描述、丙型肝炎病毒研究的第一个模型的发展和多个丙型肝炎病毒受体的鉴定。虽然在过去30年中基础免疫学研究的重大进展导致了许多医学进展，但需要对诱导免疫所涉及的协调分子机制有更实质性的了解，才能进行明智的疫苗设计，特别是针对目前尚不存在疫苗的疾病。这项建议的目的是利用合作实验室在免疫和传染病方面的广泛专业知识，以确定关键成分，如树突状细胞、T滤泡辅助细胞、单核细胞和免疫复合体在产生和维持对感染性病原体的有效免疫反应中的作用。

DESCRIPTION (provided by applicant): The goal of this program is to perform directed investigations into the evolution of lasting, protective Immune responses in humans in order to better understand the requirements of effective vaccines and adjuvants. This application is submitted to obtain funding for a Cooperative Center on Human Immunology at The Rockefeller University. Our program is highly integrated and is based on long-term, productive collaborations between the PIs on defining underlying principles of human immunology, utilizing the infrastructure of the Rockefeller University Hospital, the Zanvil Cohn Vaccine Center and the Rockefeller University Clinical and Translational Science Award (CTSA). The proposed research projects are designed as hypothesis-testing, mechanistic studies, examining novel aspects of the activation and regulation of human immune responses in the context of vaccination against infectious disease. The participating investigators are pioneers in identifying and characterizing basic mechanisms of the human immune response, having contributed to the initial characterizations of the dendritic cell, the diversity of IgG antibody effector functions ad description of Fc receptors as mediators of immunity, the development of the first models for study of the hepatitis C virus and the Identification of multiple HCV receptors. While significant progress in basic immunology research over the last three decades has resulted in numerous medical advances, a much more substantial understanding of coordinated molecular mechanisms involved in eliciting Immunity will be required to enable judicious vaccine design, particularly for diseases for which no vaccines currently exits. The objective of this proposal is o draw on the broad expertise in immunity and infectious diseases within the collaborating laboratories to define the contributions of critical components, such as dendritic cells, T follicuar helper cells, monocytes and immune complexes in the generation and maintenance of effective immune responses to infectious agents.