NONHUMAN PRIMATE MODELS FOR PANDEMIC INFLUENZA VACCINES

用于大流行性流感疫苗的非人类灵长类动物模型

• 批准号: 8173125
• 负责人: Thomas C. Friedrich
• 金额: $ 4.13万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173125
• 关键词: Acquired Immunodeficiency Syndrome; Animals; Birds; Blood; Complex; Computer Retrieval of Information on Scientific Projects Database; Cytotoxic T-Lymphocytes; Data; Epitopes; Foundations; Funding; Grant; HIV; Immune response; Immunity; Immunology; Infection; Influenza; Influenza A Virus, H1N1 Subtype; Institution; Knowledge; Lung; Macaca; Macaca mulatta; Major Histocompatibility Complex; Maps; Mind; Modeling; Population; Research; Research Personnel; Resources; Role; Services; Source; T-Lymphocyte Epitopes; United States National Institutes of Health; Virus; Virus Diseases; combat; cost; design; improved; influenza virus strain; influenza virus vaccine; influenzavirus; nonhuman primate; pandemic disease; pandemic influenza; prevent; response; seasonal influenza; vaccine evaluation; virology

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: To greatly improve the nonhuman primate model for influenza. In the last decade, new pathogenic strains of influenza virus (H5N1) have emerged and spread rapidly among bird populations. Over 200 people have been infected by these viruses, and about 60% of them have died. This project aims to greatly improve the nonhuman primate model for influenza, which will enable researchers to design and test vaccines to prevent a potentially deadly pandemic. Knowledge of the epitopes recognized by cytotoxic T lymphocytes (CTL) and their restricting major histocompatibility complex class I (MHC-I) molecules has made possible major advances in the understanding of immunity to AIDS viruses in the macaque model. However, despite the utility of the macaque model for AIDS research, macaques have been underutilized in research into other devastating viral diseases. For example, almost nothing is known about the importance of CTL in combating pathogenic influenza in higher animals. As a first step toward understanding cellular immune responses to influenza, we have inoculated 12 rhesus and 2 cynomolgus macaques with a seasonal influenza virus and tracked the induction of cellular immune responses. Our data suggest that CTL responses are rapidly induced upon infection and are readily detectable both in the lung and in blood. We are currently mapping minimal optimal CTL epitopes recognized by these animals and plan to begin producing the first influenza epitope MHC-I tetrameric complexes by mind-2010. We are also determining whether CTL can protect animals against challenge with the 2009 pandemic H1N1 virus. This project will therefore help determine the role of CTL in immunity to newly emerging pandemic influenza viruses, and will provide a foundation of preliminary data necessary to apply for NIH funds with which to examine immunity to pandemic influenza in more depth. This research uses WNPRC Immunology & Virology Services. Note: Not AIDS related, but key words similar. This research is funded through Dr. Friedrich's UW-Madison ICTR no-cost extension, and also highly relates to Dr. Kawaoka's funding of research on pandemic influenzas.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 目的：改进非人灵长类动物流感模型。 在过去十年中，出现了新的致病性流感病毒株（H5 N1），并在鸟类种群中迅速传播。 超过200人感染了这些病毒，其中约60%已经死亡。 该项目旨在大大改善非人类灵长类动物流感模型，这将使研究人员能够设计和测试疫苗，以防止潜在的致命大流行。 细胞毒性T淋巴细胞（CTL）及其限制性主要组织相容性复合物I类（MHC-I）分子识别的表位的知识，使得在猕猴模型中对艾滋病病毒免疫的理解可能取得重大进展。 然而，尽管猕猴模型用于艾滋病研究，猕猴在其他破坏性病毒性疾病的研究中未得到充分利用。例如，人们对CTL在高等动物中对抗致病性流感的重要性几乎一无所知。 作为了解流感细胞免疫反应的第一步，我们用季节性流感病毒接种了12只恒河猴和2只食蟹猴，并跟踪了细胞免疫反应的诱导。 我们的数据表明，在感染后迅速诱导CTL应答，并且在肺和血液中容易检测到。 我们目前正在绘制这些动物识别的最小最佳CTL表位，并计划在mind-2010之前开始产生第一个流感表位MHC-I四聚体复合物。 我们还在确定CTL是否可以保护动物免受2009年H1N1大流行病毒的攻击。 因此，该项目将有助于确定CTL在对新出现的大流行性流感病毒的免疫中的作用，并将为申请NIH基金提供必要的初步数据基础，以更深入地研究对大流行性流感的免疫。 这项研究使用WNPRC免疫学和病毒学服务。 注：与艾滋病无关，但关键词相似。 这项研究是由弗里德里希博士的威斯康星大学麦迪逊分校国际刑事法庭免费扩展资助的，也与河冈博士对大流行性流感研究的资助密切相关。