The overall objective for this core (Core A: Pre-clinical Trials and Pathology) are to provide the required experimental animals and support services needed to facilitate the AIDS vaccine development studies proposed in Projects 1-4 in this application. This will include provision of 2-3 year old retrovirus-free (SIV, STLV-1, SRV) rhesus macaques from the Yerkes macaque breeding colonies; immunization of the animals with DNA or protein immunogens as detailed in Projects 1 and 2; intravenous viral challenges of selected immunized animals; daily monitoring of the experimental animals; periodic physical examinations, blood collections and lymph node biopsies from the experimental animals to assess the animals' clinical and physical condition and to provide specimens for laboratory evaluations (Projects 1-4); performance of CBCs and flow cytometry evaluations to determine lymphocyte subsets; RT-QC-PCR determination to evaluate viral load in the plasma of immunized challenged animals; viral cultures of PBMCs of immunized, challenged animals to determine if the vaccines were effective in preventing infection; performance of in situ hybridization and/or immunohistochemistry studies of specimens collected by biopsy or at necropsy of immunized, challenged animals; and the performance of complete gross and histologic evaluation of all experimental animals that die or that are sacrificed during the course of the study. Provision of these resources and support services will facilitate the development and testing of AIDS vaccines as described in Projects 1-4 of this application. The virological, immunologic and clinico-pathologic evaluations proposed will allow an assessment of vaccine efficacy with respect to either the prevention of infection (sterilizing immunity) or modification of post-challenge virus load or viral set point.
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