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: Because the most devastating pathogens likely to be used as biological weapons are those that infect an individual via the respiratory tract, this subcontract to UCD encompasses studies to directly test the ability of respiratory tract CpG administration to raise the in-vivo resistance to respiratory viral pathogens in primate models. We also propose to define the mechanisms by which CpGs elicit enhanced antiviral resistance. The unifying hypothesis of all the studies in this subcontract is that CpGs enhance both the innate non-specific anti-viral responses and the adaptive and specific immune response to a pathogen. Thus, we propose that in CpG-treated animals there will be a more rapid induction of innate antiviral responses that, when combined with the more rapid and robust adaptive antiviral cellular responses, there will be attenuated infection and enhanced resistance to clinical viral disease compared to CpG na ve animals. This hypothesis will be tested in two primate viral infection models that use the highly contagious human respiratory viral pathogens, measles virus and Type A influenza virus and in mice infected with influenza A. The effect of CpG administration on lymphoid and antigen presenting cell populations in the nasal and lower respiratory tract mucosa will be measured by multiparameter flow cytometry, cytokine gene regulation and humoral/cellular immune responses.
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