NONHUMAN PRIMATE MODELS FOR PANDEMIC INFLUENZA VACCINES

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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.