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Core B: Non-Human Primate Core

$437,658P01FY2023AINIH

University Of Washington, Seattle WA

Investigators

Abstract

NHP CORE B SUMMARY The Nonhuman Primate (NHP) Core seeks to consolidate supervision and performance of the NHP experimental protocols of the Program Project entitled “Mechanisms Programming Protective Immunity from RhCMV/SIV Vaccine and IL-15 Actions” into a structured Core composed of highly experienced research personnel. The global objective of the Core is to provide leadership and technical expertise to ensure consistency and quality control in animal selection, execution of study protocols, application of experimental procedures, animal observations and data collection necessary to meet the objectives of Project and other Core lead investigators. To accomplish this, the Core will manage and directly supervise all NHP studies for the Project including: 1) animal selection; 2) animal housing and general husbandry; 3) experimental procedures and clinical management; 4) specimen collection and processing; 5) necropsy studies; and 6) acquisition and management of animal demographic, physiologic, clinical, and pathologic data. The overall objective of the Program Project is to determine the systems response to RhCMV/SIV vaccination and the role of IL-15 signaling in programming vaccine-induced immune responses responsible for complete arrest and subsequent clearance of SIV infection in RhCMV/SIV-immunized rhesus macaques. The NHP Core will provide the expertise and technical support required to ensure successful completion of the six multifaceted and extensive NHP experimental protocols supporting the 2 projects proposed in this Program. These studies are designed to: a) determine systemic transcriptomic correlates of the RhCMV/SIV vaccine-induced whole blood Protection-Predictive Transcriptomic Signature [wbPPTS] in peripheral and mucosal lymphoid tissues and its dependence on IL-15 signaling (Project 1); b) define specific spatial transcriptomic response to RhCMV/SIV-infected cells in tissues and identify the direct contribution of vector-infected cells to the local and systemic transcriptomic responses linked to wbPPTS programming (Project 1); c) determine the mechanisms underlying the association between IL-15 signaling quiescence and generation of the wbPPTS (Project 1) and d) link the tissue and blood transcriptomic programming identified is a-c to IL-15 signaling pathways, RhCMV/SIV vaccine efficacy and the larger vaccine response landscape in NHP and people (Project 2).

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