The Indian rhesus macaque develops a disease that closely mimics human acquired immunodeficiency syndrome (AIDS) when infected by simian immunodeficiency virus (SIV) or chimeric simian-human immunodeficiency viruses (SHIV), and represents the best animal model for HIV infection. Because of the similarity of the immune systems of macaques and humans, preclinical vaccine development is heavily dependent on the SIV and SHIV macaque models. Their research value notwithstanding, nonhuman primates (NHPs) are complex, higher order species that require specialized infrastructure and expertise in a research setting. The NHP Core seeks to consolidate the experimental animal and cellular immunology portions of the HIV Vaccine Research and Design (HIVRAD) Program project, """"""""Programming HIV Immune Response for Broadly Neutralizing Antibodies by Vaccination"""""""" into a single Core composed of highly experienced professional and technical personnel and state-of-the-art resources. The NHP Core, functioning within the Oregon National Primate Research Center (ONPRC), will provide infrastructure and professional and technical expertise for the NHP experimental protocol and the antigen (Ag)-specific CD4+ and CD8+ T cell analyses supporting the """"""""HIV Quasispecies Vaccine Immunogenicity and SHIV Challenge Study"""""""".
The Specific Aims are: 1) to provide specialized expertise and infrastructure for comprehensive, efficient and safe conduct of the nonhuman primate-related portions of the HIVRAD Program including animal selection, research protocol implementation and execution, sample acquisition and distribution, animal care, and project budget administration, and 2) to provide the HIVRAD Program with flow cytometric assays of Ag- specific T cell immunity and SHIV immunopathogenesis. The immune monitoring section of the Nonhuman Primate Core will provide sophisticated assays of SIV/HIV-specific T cell immunity (polychromatic cytokine flow cytometry) and SHIV immunopathogenesis (polychromatic phenotypic analysis) of SHIV target cell dynamics in blood and tissue.

Public Health Relevance

A safe and effective vaccine remains the best hope of controlling the human immunodeficiency virus (HIV) pandemic. The studies in this proposal focus on developing vaccine strategies to promote broadly neutralizing anti-HIV antibody, a key component of the host immune response against HIV that may prevent infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI078064-04
Application #
8377538
Study Section
Special Emphasis Panel (ZAI1-EC-A)
Project Start
Project End
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
4
Fiscal Year
2012
Total Cost
$333,412
Indirect Cost
$44,172
Name
Oregon Health and Science University
Department
Type
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Nicholas, Katherine J; Flaherty, David K; Smith, Rita M et al. (2017) Chronic HIV-1 Infection Impairs Superantigen-Induced Activation of Peripheral CD4+CXCR5+PD-1+ Cells, With Relative Preservation of Recall Antigen-Specific Responses. J Acquir Immune Defic Syndr 74:72-80
Nicholas, Katherine J; Greenplate, Allison R; Flaherty, David K et al. (2016) Multiparameter analysis of stimulated human peripheral blood mononuclear cells: A comparison of mass and fluorescence cytometry. Cytometry A 89:271-80
Hessell, Ann J; Malherbe, Delphine C; Pissani, Franco et al. (2016) Achieving Potent Autologous Neutralizing Antibody Responses against Tier 2 HIV-1 Viruses by Strategic Selection of Envelope Immunogens. J Immunol 196:3064-78
Hessell, Ann J; Haigwood, Nancy L (2015) Animal models in HIV-1 protection and therapy. Curr Opin HIV AIDS 10:170-6
Sather, D Noah; Carbonetti, Sara; Malherbe, Delphine C et al. (2014) Emergence of broadly neutralizing antibodies and viral coevolution in two subjects during the early stages of infection with human immunodeficiency virus type 1. J Virol 88:12968-81
Cohen, Kristen; Altfeld, Marcus; Alter, Galit et al. (2014) Early preservation of CXCR5+ PD-1+ helper T cells and B cell activation predict the breadth of neutralizing antibody responses in chronic HIV-1 infection. J Virol 88:13310-21
Malherbe, Delphine C; Pissani, Franco; Sather, D Noah et al. (2014) Envelope variants circulating as initial neutralization breadth developed in two HIV-infected subjects stimulate multiclade neutralizing antibodies in rabbits. J Virol 88:12949-67
Pissani, Franco; Malherbe, Delphine C; Schuman, Jason T et al. (2014) Improvement of antibody responses by HIV envelope DNA and protein co-immunization. Vaccine 32:507-13
Nicholas, Katherine J; Zern, Emily K; Barnett, Louise et al. (2013) B cell responses to HIV antigen are a potent correlate of viremia in HIV-1 infection and improve with PD-1 blockade. PLoS One 8:e84185
Pissani, Franco; Malherbe, Delphine C; Robins, Harlan et al. (2012) Motif-optimized subtype A HIV envelope-based DNA vaccines rapidly elicit neutralizing antibodies when delivered sequentially. Vaccine 30:5519-26

Showing the most recent 10 out of 11 publications