NONHUMAN PRIMATE MODELS FOR PANDEMIC INFLUENZA VACCINES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目的：对非人灵长类流感动物模型进行较大改进。 在过去的十年中，出现了新的致病毒株(H5N1)，并在禽类中迅速传播。已有200多人感染了这些病毒，其中约60%死亡。该项目旨在大幅改进非人类灵长类流感模型，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)识别的表位及其限制性主要组织相容性复合体I类(MHC-I)分子的认识，使得在猕猴模型中理解对艾滋病病毒的免疫有可能取得重大进展。然而，尽管猕猴模型在艾滋病研究中很有用，但猕猴在其他破坏性病毒疾病的研究中一直没有得到充分利用。例如，对于CTL在高等动物中对抗致病性流感的重要性，人们几乎一无所知。作为了解流感细胞免疫反应的第一步，我们给两只恒河猴和两只食蟹猴接种了季节性流感病毒，并跟踪了细胞免疫反应的诱导。我们的初步数据表明，CTL反应在感染后迅速诱导，在肺和血液中都很容易检测到。我们下一阶段的研究将确定这些CTL是否能够保护动物免受季节性流感病毒不同毒株的攻击。因此，该项目将有助于确定CTL在灵长类动物流感免疫中的作用，并将为申请NIH资金提供必要的初步数据基础，以充分开发NHP流感模型。 注：本项目中的物种也包括短尾猴。 注：与艾滋病无关，但关键词相似。

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 2 rhesus and 2 cynomolgus macaques with a seasonal influenza virus and tracked the induction of cellular immune responses. Our preliminary data suggest that CTL responses are rapidly induced upon infection and are readily detectable both in the lung and in blood. The next phase of our study will determine whether these CTL can protect animals against challenge with a divergent strain of seasonal influenza virus. This project will therefore help determine the role of CTL in immunity to influenza in primates, and will provide a foundation of preliminary data necessary to apply for NIH funds with which to fully develop the NHP model of influenza. Note: Species on this project include Macaca fascicularis as well. Note: Not AIDS related, but key words similar.