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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project with Complex Structure Cooperative Agreement (UM1)
Project #
Application #
Study Section
Special Emphasis Panel (ZAI1)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Scripps Research Institute
La Jolla
United States
Zip Code
Scheid, Johannes F; Horwitz, Joshua A; Bar-On, Yotam et al. (2016) HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption. Nature 535:556-60
Barton, John P; Goonetilleke, Nilu; Butler, Thomas C et al. (2016) Relative rate and location of intra-host HIV evolution to evade cellular immunity are predictable. Nat Commun 7:11660
Briney, Bryan; Sok, Devin; Jardine, Joseph G et al. (2016) Tailored Immunogens Direct Affinity Maturation toward HIV Neutralizing Antibodies. Cell 166:1459-1470.e11
Landais, Elise; Huang, Xiayu; Havenar-Daughton, Colin et al. (2016) Broadly Neutralizing Antibody Responses in a Large Longitudinal Sub-Saharan HIV Primary Infection Cohort. PLoS Pathog 12:e1005369
van Gils, Marit J; van den Kerkhof, Tom L G M; Ozorowski, Gabriel et al. (2016) An HIV-1 antibody from an elite neutralizer implicates the fusion peptide as a site of vulnerability. Nat Microbiol 2:16199
Moldt, Brian; Le, Khoa; Carnathan, Diane G et al. (2016) Neutralizing antibody affords comparable protection against vaginal and rectal SHIV challenge in macaques. AIDS :
Lu, Ching-Lan; Murakowski, Dariusz K; Bournazos, Stylianos et al. (2016) Enhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo. Science 352:1001-4
Tam, Hok Hei; Melo, Mariane B; Kang, Myungsun et al. (2016) Sustained antigen availability during germinal center initiation enhances antibody responses to vaccination. Proc Natl Acad Sci U S A 113:E6639-E6648
Havenar-Daughton, Colin; Carnathan, Diane G; Torrents de la Peña, Alba et al. (2016) Direct Probing of Germinal Center Responses Reveals Immunological Features and Bottlenecks for Neutralizing Antibody Responses to HIV Env Trimer. Cell Rep 17:2195-2209
Dan, Jennifer M; Lindestam Arlehamn, Cecilia S; Weiskopf, Daniela et al. (2016) A Cytokine-Independent Approach To Identify Antigen-Specific Human Germinal Center T Follicular Helper Cells and Rare Antigen-Specific CD4+ T Cells in Blood. J Immunol 197:983-93

Showing the most recent 10 out of 206 publications