? Nonhuman Primate (NHP) Core (Core 1) The primary gap impeding development of an effective vaccine to prevent congenital CMV (cCMV) is the lack of understanding of the immune responses that are required for protection of the fetus against cCMV transmission and disease. A clear understanding of the immunologic and virologic factors that impact cCMV outcome requires application of highly-relevant animal models that both closely mimic human fetal disease and can be immunologically modulated. To guide the development of an effective vaccine against cCMV, this Program proposes to utilize a novel NHP model of cCMV infection - placental transmission of RhCMV of pregnant rhesus monkey dams? to define the maternal virus-specific immune responses and properties of the virus populations that impact cCMV infection. Due to the highly technical requirements of these studies and limited availability to RhCMV seronegative breeding age females, implementation of these RhCMV challenge studies in pregnant dams requires multiple levels of coordination and oversight. Thus, we propose to establish a centralized Nonhuman Primate (NHP) Core, which will coordinate all maternal/fetal NHP experiments, samples, and data between two national Primate Research Centers (Tulane National Primate Research Center and California National Primate Research Center) and the Program's Projects 1&2. Specifically, the NHP Core will support this Program through the following Specific Aims:
Aim 1 : Coordinate management of breeding-age, RhCMV-seronegative female rhesus monkeys to enable maternal/fetal rhesus monkey studies (Projects 1&2);
Aim 2 : Organize, coordinate, and oversee maternal/fetal rhesus monkey studies and sample distribution (Projects 1&2, Core 2&3), and Aim 3: Produce, characterize, and monitor levels in vivo of standardized RhCMV hyperimmune globulin (HIG) from RhCMV-seropositive monkeys to be used for passive infusion of natural maternal anti-RhCMV antibody to understand the impact of viral Fc receptors on placental transmission and fetal pathogenesis (Project 2). Oversight and sample and data management support provided by the NHP Core is essential for the overall Program to achieve the shared goals of defining the immunologic and virologic determinants of cCMV transmission which will provide immunologic targets for vaccine design to eliminate cCMV infection.
