This resource provides unique primate reagents not available commercially in support of NIH funded investigators using nonhuman primates (NHP) as pre-clinical models for vaccine efficacy and immunotherapies. Hence, the rationale for this application. State of the art investigations of immune responses related to human infectious diseases, autoimmune diseases, organ and cell allogeneic and xenogeneic transplantation models or immunization procedures that use nonhuman primate models increasingly include the use of recombinant cytokines, chemokines, growth factors or immunomodulatory ligands in vivo. While the close evolutionary relationship between human and nonhuman primates results in cross reactivity between most human recombinant factors when used with NHP cells, differences in affinity/bioactivity have been noted. More important however, most if not all nonhuman primate molecules are not identical to human homologues, often leading to the development of neutralizing antibody responses to the xenogeneic molecule in vivo, potentially providing uninterpretable data and markedly restricting the repeated and most optimal in vivo use of select immunomodulators in these models. Clearly, the availability of well characterized and standardized purified recombinant NHP reagents including the ones produced and distributed by the NCRR funded """"""""Resource for Nonhuman Primate Immune Reagents"""""""" has largely alleviated this limitation and allowed numerous investigators to address seminal questions using nonhuman primates during the past 3 years of funding as attested by the support letters of such recipients (Appendix). In addition, a number of candidate vaccines against several agents classified as bioterrorism categories A-C by the NIH/NIAID and CDC are at stages ready to be tested for efficacy in NHP. Investigators planning to test such candidate vaccines have already approached us regarding the feasibility of incorporating one or more reagents as potential adjuvants to broaden or potentiate immune responses. Thus, this application requests continued support for allowing this Resource to continue to provide NHP cytokines/chemokines/soluble co-stimulatory factors, DNA constructs capable of expressing such factors and explore strategies for improving the pharmacokinetics and biological effects of such reagents in vivo. Specifically, the resource will perform the following: 1. Preparation, testing and distribution of NHP cytokines/chemokines. 2. Construction and testing of optimized plasmid based constructs for the expression of NHP cytokines/chemokines and immunomodulatory factors.
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