Non Human Primate Models of SIV and HIV Immune Protection

Mascola, John

Abstract

Antibodies against HIV are potential drugs that may be able to prevent HIV infection in humans. However, the long-term protective capacity of antibodies against HIV has not been assessed. In this study, we repetitively administered a macaque version of a human anti-HIV antibody to monkeys, after which the antibody persisted in the blood for >5 months. Moreover, the antibody could be sustained at protective levels for 108 days, conferring protection 52 days after the last dose in a monkey model of HIV infection. Thus, passive antibody transfer can provide durable protection against infection by viruses that cause AIDS in primates.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Investigator-Initiated Intramural Research Projects (ZIA)
• Project #: 1ZIAAI005009-14
• Application #: 9161743
• Support Year: 14
• Fiscal Year: 2015

Institution

• Name: Niaid Extramural Activities

Publications

Hessell, Ann J; Jaworski, J Pablo; Epson, Erin et al. (2016) Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in infant macaques. Nat Med 22:362-8

Bolton, Diane L; Pegu, Amarendra; Wang, Keyun et al. (2016) Human Immunodeficiency Virus Type 1 Monoclonal Antibodies Suppress Acute Simian-Human Immunodeficiency Virus Viremia and Limit Seeding of Cell-Associated Viral Reservoirs. J Virol 90:1321-32

Gautam, Rajeev; Nishimura, Yoshiaki; Pegu, Amarendra et al. (2016) A single injection of anti-HIV-1 antibodies protects against repeated SHIV challenges. Nature 533:105-109

Saunders, Kevin O; Pegu, Amarendra; Georgiev, Ivelin S et al. (2015) Sustained Delivery of a Broadly Neutralizing Antibody in Nonhuman Primates Confers Long-Term Protection against Simian/Human Immunodeficiency Virus Infection. J Virol 89:5895-903

Ko, Sung-Youl; Pegu, Amarendra; Rudicell, Rebecca S et al. (2014) Enhanced neonatal Fc receptor function improves protection against primate SHIV infection. Nature 514:642-5

Rudicell, Rebecca S; Kwon, Young Do; Ko, Sung-Youl et al. (2014) Enhanced potency of a broadly neutralizing HIV-1 antibody in vitro improves protection against lentiviral infection in vivo. J Virol 88:12669-82

Pegu, Amarendra; Yang, Zhi-yong; Boyington, Jeffrey C et al. (2014) Neutralizing antibodies to HIV-1 envelope protect more effectively in vivo than those to the CD4 receptor. Sci Transl Med 6:243ra88

Flatz, Lukas; Cheng, Cheng; Wang, Lingshu et al. (2012) Gene-based vaccination with a mismatched envelope protects against simian immunodeficiency virus infection in nonhuman primates. J Virol 86:7760-70

Gautam, Rajeev; Nishimura, Yoshiaki; Lee, Wendy R et al. (2012) Pathogenicity and mucosal transmissibility of the R5-tropic simian/human immunodeficiency virus SHIV(AD8) in rhesus macaques: implications for use in vaccine studies. J Virol 86:8516-26

Yeh, Wendy W; Brassard, Laura M; Miller, Caroline A et al. (2012) Envelope variable region 4 is the first target of neutralizing antibodies in early simian immunodeficiency virus mac251 infection of rhesus monkeys. J Virol 86:7052-9