The long-range goal of this Program Project is to develop vaccine strategies against mucosal SIV (and HIV in the future) transmission, with a special focus on identifying local and systemic mechanisms leading to protective B cell development and antibody production. The objectives for the Primate Core are to provide the experimental animals and support services needed to facilitate the efficient completion of the aims outlined in Project 1, 2, 3 and 4. This will include the provision of retrovirus-free adult female rhesus macaques from the Yerkes rhesus macaque breeding colonies;immunizations using the various immunization platforms (Projects 1 and 2) sample collections (for all projects) and repeated low dose vaginal challenges with SIVsmE660. The Primate Core tasks also include daily monitoring ofthe experimental animals;periodic physical examinations with blood collections for immunologic and virologic evaluations and procurement/shipment of samples to the Program Project investigators;the performance of CBCs and laboratory analyses as needed;Perform euthanasia with sample collection and processing for Projects 3 and 4;and the performance of a basic gross and histologic necropsy evaluations of all experimental animals that die or are sacrificed during the course of this study. Provision of these resources and support services will facilitate the development and testing of novel AIDS vaccine concepts proposed in this Program Project. The Primate Core will play a key role in the development of a vaccine to prevent mucosal transmission and pathogenicity of SIV and HIV and the determination Of correlates of such protection. Vaccine efficacy will be evaluated by its ability to 1) prevent acquisition of infection (sterilizing immunity) or 2) significant control of viremia post-challenge and preservation of protective immune responses.
This program will expand 2 promising SIV vaccine platforms as a preclinical model for an efficient HIV vaccine. In addition the experimental design ofthe primate experiment will also allow for detailed investigations into the mechanisms that contribute to this protection versus those that do not. To this end, the primate core will provide state ofthe art support in the design and conduct of primate vaccine experiments.
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|Kannanganat, Sunil; Wyatt, Linda S; Gangadhara, Sailaja et al. (2016) High Doses of GM-CSF Inhibit Antibody Responses in Rectal Secretions and Diminish Modified Vaccinia Ankara/Simian Immunodeficiency Virus Vaccine Protection in TRIM5?-Restrictive Macaques. J Immunol 197:3586-3596|
|Locci, Michela; Wu, Jennifer E; Arumemi, Fortuna et al. (2016) Activin A programs the differentiation of human TFH cells. Nat Immunol 17:976-84|
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|Cho, Alice; Wrammert, Jens (2016) Implications of broadly neutralizing antibodies in the development of a universal influenza vaccine. Curr Opin Virol 17:110-5|
|Santangelo, Philip J; Rogers, Kenneth A; Zurla, Chiara et al. (2015) Whole-body immunoPET reveals active SIV dynamics in viremic and antiretroviral therapy-treated macaques. Nat Methods 12:427-32|
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