Infection of rhesus macaques with simian immunodeficiency virus (SIV) or simian-human immunodeficiency virus (SHIV) is a key animal model for HIV-1 infection. The Nonhuman Primate (NHP) Scientific Research Support Component (SRSC) aims to support this CHAVI-ID by providing all the expertise, infrastructure, reagents, personnel, and animals for the conduct of complex in vivo immunogenicity and challenge studies in NHPs. This SRSC will involve leadership from both Beth Israel Deaconess Medical Center and the Yerkes National Primate Research Center (Emory University) and is well positioned to meet the CHAVI-ID goals. This SRSC leadership will work closely with the research discovery teams responsible for the studies described in Scientific Foci #1 and#2 and participate actively in the scientific mission of this CHAVI-ID. The main role of this SRSC is to provide leadership and technical expertise to ensure consistency and quality control in animal selection, execution of study protocols, experimental procedures, sample acquisition and distribution, immunologic and virologic studies, and data collection and analysis.
The Specific Aims are: 1. To support this CHAVI-ID by selecting and providing rhesus macaques, providing exceptional animal care, conducting experimental studies with monoclonal antibodies (MAbs) and vaccines, collecting samples for immunologic and virologic testing, and performing necropsy studies. These studies will initially evaluate: A. Protective efficacy of HIV-1 Env-specific MAbs against SHIV challenge; B. Immunogenicity and protective efficacy of novel HIV-1 Env immunogens and immunization strategies; 2. To support this CHAVI-ID by providing blood and tissue samples from SIV/SHIV-infected and uninfected NHPs to collaborating investigators to underpin basic research studies. These samples will support studies of neutralizing Abs in Focus #1 and will help elucidate the characteristics of virus-specific CD4+ follicular helper T cell (Tfh) responses in Focus #2, with an initial emphasis on the development of Tfh cells during vaccine-induced immune responses and the role of Tfh cells in promoting the affinity maturation of antibodies.

Public Health Relevance

This Nonhuman Primate SRSC supports the CHAVI-ID by providing centralized and standardized preclinical testing of vaccine concepts. This is critical for supporting the immunogen discovery activities of the CHAVI-ID.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project with Complex Structure Cooperative Agreement (UM1)
Project #
5UM1AI100663-02
Application #
8508854
Study Section
Special Emphasis Panel (ZAI1-JBS-A)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
2
Fiscal Year
2013
Total Cost
$2,109,453
Indirect Cost
$545,903
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Sok, Devin; Doores, Katie J; Briney, Bryan et al. (2014) Promiscuous glycan site recognition by antibodies to the high-mannose patch of gp120 broadens neutralization of HIV. Sci Transl Med 6:236ra63
Murin, Charles D; Julien, Jean-Philippe; Sok, Devin et al. (2014) Structure of 2G12 Fab2 in complex with soluble and fully glycosylated HIV-1 Env by negative-stain single-particle electron microscopy. J Virol 88:10177-88
Scharf, Louise; Scheid, Johannes F; Lee, Jeong Hyun et al. (2014) Antibody 8ANC195 reveals a site of broad vulnerability on the HIV-1 envelope spike. Cell Rep 7:785-95
Doria-Rose, Nicole A; Schramm, Chaim A; Gorman, Jason et al. (2014) Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies. Nature 509:55-62
Tong, Tommy; Crooks, Ema T; Osawa, Keiko et al. (2014) Multi-parameter exploration of HIV-1 virus-like particles as neutralizing antibody immunogens in guinea pigs, rabbits and macaques. Virology 456-457:55-69
Li, Shuzhao; Rouphael, Nadine; Duraisingham, Sai et al. (2014) Molecular signatures of antibody responses derived from a systems biology study of five human vaccines. Nat Immunol 15:195-204
Gitlin, Alexander D; Shulman, Ziv; Nussenzweig, Michel C (2014) Clonal selection in the germinal centre by regulated proliferation and hypermutation. Nature 509:637-40
Pulendran, Bali (2014) Systems vaccinology: probing humanity's diverse immune systems with vaccines. Proc Natl Acad Sci U S A 111:12300-6
Bates, John T; Keefer, Christopher J; Slaughter, James C et al. (2014) Escape from neutralization by the respiratory syncytial virus-specific neutralizing monoclonal antibody palivizumab is driven by changes in on-rate of binding to the fusion protein. Virology 454-455:139-44
Sundling, Christopher; Zhang, Zhenhai; Phad, Ganesh E et al. (2014) Single-cell and deep sequencing of IgG-switched macaque B cells reveal a diverse Ig repertoire following immunization. J Immunol 192:3637-44

Showing the most recent 10 out of 58 publications