Scientific Research Support Component C/Non- Human Primates

Barouch, Dan H.

Abstract

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.

Funding Agency

• 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)
• 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

Institution

• Name: Scripps Research Institute
• DUNS #: 781613492
• City: La Jolla
• State: CA
• Country: United States
• Zip Code: 92037

Publications

Rantalainen, Kimmo; Berndsen, Zachary T; Murrell, Sasha et al. (2018) Co-evolution of HIV Envelope and Apex-Targeting Neutralizing Antibody Lineage Provides Benchmarks for Vaccine Design. Cell Rep 23:3249-3261

Bar-On, Yotam; Gruell, Henning; Schoofs, Till et al. (2018) Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals. Nat Med 24:1701-1707

Watanabe, Yasunori; Raghwani, Jayna; Allen, Joel D et al. (2018) Structure of the Lassa virus glycan shield provides a model for immunological resistance. Proc Natl Acad Sci U S A 115:7320-7325

Allen, Joel D; Sanders, Rogier W; Doores, Katie J et al. (2018) Harnessing post-translational modifications for next-generation HIV immunogens. Biochem Soc Trans 46:691-698

Gautam, Rajeev; Nishimura, Yoshiaki; Gaughan, Natalie et al. (2018) A single injection of crystallizable fragment domain-modified antibodies elicits durable protection from SHIV infection. Nat Med 24:610-616

Young, Gavin; Hundt, Nikolas; Cole, Daniel et al. (2018) Quantitative mass imaging of single biological macromolecules. Science 360:423-427

Dosenovic, Pia; Kara, Ervin E; Pettersson, Anna-Klara et al. (2018) Anti-HIV-1 B cell responses are dependent on B cell precursor frequency and antigen-binding affinity. Proc Natl Acad Sci U S A 115:4743-4748

Richard, Jonathan; Prévost, Jérémie; Baxter, Amy E et al. (2018) Uninfected Bystander Cells Impact the Measurement of HIV-Specific Antibody-Dependent Cellular Cytotoxicity Responses. MBio 9:

Abbott, Robert K; Lee, Jeong Hyun; Menis, Sergey et al. (2018) Precursor Frequency and Affinity Determine B Cell Competitive Fitness in Germinal Centers, Tested with Germline-Targeting HIV Vaccine Immunogens. Immunity 48:133-146.e6

Pauthner, Matthias G; Nkolola, Joseph P; Havenar-Daughton, Colin et al. (2018) Vaccine-Induced Protection from Homologous Tier 2 SHIV Challenge in Nonhuman Primates Depends on Serum-Neutralizing Antibody Titers. Immunity :