Integrating innate and adaptive pathways in vaccine responses

描述（由申请方提供）：本项目的目标是对人类持久保护性免疫应答的演变进行定向研究，以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，是基于长期的，富有成效的合作PI之间的定义人类免疫学的基本原则，利用洛克菲勒大学医院，Zanvil Cohn疫苗中心和洛克菲勒大学临床和转化科学奖（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，研究在接种传染病疫苗的背景下人类免疫反应的激活和调节的新方面。参与的研究人员是识别 并表征了人类免疫应答的基本机制，对树突状细胞的初步表征、IgG抗体效应子功能的多样性和作为免疫介质的Fc受体的描述、用于研究丙型肝炎病毒的第一个模型的开发和多种HCV受体的鉴定做出了贡献。虽然在过去的三十年中，基础免疫学研究取得了重大进展，导致了许多医学进步，但需要对引发免疫的协调分子机制有更深入的了解，才能进行明智的疫苗设计，特别是对于目前没有疫苗的疾病。本提案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，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物）在产生和维持对传染性病原体的有效免疫应答中的作用。

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.