Studies in non-human primates (NHPs) have made substantial contributions to our understanding of HIV-1 pathogenesis and vaccine immunology. The high overall genetic homology between humans and rhesus macaques, coupled with the phenotypic conservation of lymphocyte populations, highlights the utility of NHPs for evaluating clinical vaccine candidates. Core B will be responsible for the planning, design and execution of non-human primate (NHP) experiments described in Projects 1-4 of this HIVRAD P01. Additionally, the Core will support the dissemination of NHP cells, plasma, DNA and cloned antibodies to Project 1-4 as required to meet the overall goals ofthe HIVRAD consortia. In addition, the Core will support sample distribution to relevant collaboration partners, to maximize the information gained from these studies.
In Aim 1, Core B will provide the necessary logistical support for the NHP experiments such as complete the appropriate papenwork for conducting NHP studies at the Astrid Fagraeus Laboratory (AFL) in Stockholm, plan the purchase and transport ofthe rhesus macaques and their housing organization. Core B will also serve as a communication link between Projects 1-4 and the NIH for all issues related to the NHP immunogenicity studies to support the efforts of all Projects within the proposal.
In Aim 2, Core B will oversee the execution ofthe NHP experiments to be conducted in this proposal, including ensuring that detailed schedules for inoculations and sample collection exist as well as robust processes to maintain the NHP biobank.
In Aim 3, Core B will work with the personnel at the AFL to refine methods for B cell sampling and analysis of humoral immune responses. The proximity between the AFL and the Karisson Hedestam laboratory means that vaccine components can be prepared immediately before animal inoculation and hand-delivered directly to the AFL. Similariy, transfer of cells from the animals back to the laboratory is performed by personnel in the Karlsson Hedestam laboratory who collect PBMCs, bone marrow, lymph node biopsies directly from the AFL for direct analysis or freezing back in the Karisson Hedestam laboratory. These processes are of critical importance forthe success ofthe proposed HIVRAD project.

Public Health Relevance

The major objective of Core B is to conduct the non-human primate experiments required to address the questions outlined in Projects 1-4 of this HIVRAD application. The ultimate aims of these studies are to define, at a high resolution, Env vaccine-elicited B cell responses and to use this information to design new generation Env vaccine candidates to more successfully elicit broadly protective B cell responses against HlV-1

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program Projects (P01)
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Special Emphasis Panel (ZAI1-KP-A (J1))
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Scripps Research Institute
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Ingale, Jidnyasa; Stano, Armando; Guenaga, Javier et al. (2016) High-Density Array of Well-Ordered HIV-1 Spikes on Synthetic Liposomal Nanoparticles Efficiently Activate B Cells. Cell Rep 15:1986-99
Longo, Nancy S; Sutton, Matthew S; Shiakolas, Andrea R et al. (2016) Multiple Antibody Lineages in One Donor Target the Glycan-V3 Supersite of the HIV-1 Envelope Glycoprotein and Display a Preference for Quaternary Binding. J Virol 90:10574-10586
Wang, Yimeng; Sundling, Christopher; Wilson, Richard et al. (2016) High-Resolution Longitudinal Study of HIV-1 Env Vaccine-Elicited B Cell Responses to the Virus Primary Receptor Binding Site Reveals Affinity Maturation and Clonal Persistence. J Immunol 196:3729-43

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