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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 目的：大大改善了流感的非人类灵长类动物模型。 在过去的十年中，流感病毒（H5N1）的新致病菌株已经出现并在鸟类种群中迅速传播。 这些病毒已经感染了200多人，其中约60％的人死亡。 该项目旨在大大改善流感的非人类灵长类动物模型，该模型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。 了解通过细胞毒性T淋巴细胞（CTL）识别的表位及其限制了主要的组织相容性复合物I类（MHC-I）分子的知识，这在理解猕猴模型中艾滋病病毒的免疫方面已成为可能的重大进展。 然而，尽管猕猴模型用于艾滋病研究，但猕猴在对其他毁灭性病毒疾病的研究中的利用不足。例如，几乎一无所知，关于CTL在对抗高等动物中的致病性流感方面的重要性。 作为理解细胞免疫反应对流感的第一步，我们用季节性流感病毒接种了12种恒河猴和2个cynomolgus猕猴，并跟踪了细胞免疫反应的诱导。 我们的数据表明，感染后CTL反应会迅速诱导，并且在肺和血液中很容易检测到。 目前，我们正在绘制这些动物认可的最低最佳CTL表位，并计划开始生产Mind-2010的第一个流感表位MHC-I四聚体复合物。 我们还确定CTL是否可以保护动物免受2009年大流行H1N1病毒的挑战。 因此，该项目将有助于确定CTL对新出现的大流行性流感病毒免疫的作用，并为申请NIH基金所必需的初步数据提供基础，以更深入地检查对大流行性流感的免疫力。 该研究使用WNPRC免疫学和病毒学服务。 注意：与艾滋病无关，而是关键词相似。 这项研究是通过弗里德里希（Friedrich）博士的UW-Madison ICTR无成本扩展资助的，并且与Kawaoka博士对大流行性流感研究的资助高度相关。