Vaccine induction of antibodies and tissue-resident CD8(+) T cells enhances protection against mucosal SHIV-infection in young macaques

• Type of Material: Article
• Authors: Caroline Petitdemange, Emory University; Sudhir Kasturi, Emory University; Pamela A. Kozlowski, Louisiana State University; Rafiq Nabi, Louisiana State University; Claire F. Quarnstrom, University of Minnesota; Pradeep Babu Jagadeesh Reddy, Emory University; Cynthia Derdeyn, Emory University; Lori M. Spicer, Emory University; Parin Patel, Emory University; Traci Legere, Emory University; Yevgeniy O. Kovalenkov, Emory University; Celia C. Labranche, Duke University; Francois Villinger, University of Louisiana Lafayette; Mark Tomai, 3M Drug Delivery Systems; John Vasilakos, 3M Drug Delivery Systems; Barton Haynes, Duke University; C.Yong Kang, University of Western Ontario; James S. Gibbs, National Institutes of Health; Jonathan W. Yewdell, National Institutes of Health; Dan Barouch, Harvard Medical School; Jens Wrammert, Emory University; David Montefiori, Duke University; Eric Hunter, Emory University; Rama Rao Amara, Emory University; David Masopust, University of Minnesota; Bali Pulendran, Emory University
• Language: English
• Date: 2019-02-21
• Publisher: American Society for Clinical Investigation
• Publication Version: Final Published Version
• Copyright Statement: © 2019, American Society for Clinical Investigation
• Final Published Version (URL): http://dx.doi.org/10.1172/jci.insight.126047
• Title of Journal or Parent Work: JCI insight
• Volume: 4
• Issue: 4
• Grant/Funding Information: NIH grants U19 AI096187 and UM1 AI124436 ;and NIAID/NIH Contract# HHSN27201100016C.
• Keywords: YELLOW-FEVER VACCINE; RHESUS MACAQUES; Research & Experimental Medicine; HUMAN MONOCLONAL-ANTIBODIES; Science & Technology; ADJUVANT ACTIVITY; RESPONSES; CHALLENGE; EFFICACY; RECTAL SECRETIONS; Medicine, Research & Experimental; HIV; VIREMIA; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Pathology; Health Sciences, Immunology; Biology, Virology

Abstract

Antibodies and cytotoxic T cells represent 2 arms of host defense against pathogens. We hypothesized that vaccines that induce both high-magnitude CD8+ T cell responses and antibody responses might confer enhanced protection against HIV. To test this hypothesis, we immunized 3 groups of nonhuman primates: (a) Group 1, which includes sequential immunization regimen involving heterologous viral vectors (HVVs) comprising vesicular stomatitis virus, vaccinia virus, and adenovirus serotype 5-expressing SIVmac239 Gag; (b) Group 2, which includes immunization with a clade C HIV-1 envelope (Env) gp140 protein adjuvanted with nanoparticles containing a TLR7/8 agonist (3M-052); and (c) Group 3, which includes a combination of both regimens. Immunization with HVVs induced very high-magnitude Gag-specific CD8+ T cell responses in blood and tissue-resident CD8+ memory T cells in vaginal mucosa. Immunization with 3M-052 adjuvanted Env protein induced robust and persistent antibody responses and long-lasting innate responses. Despite similar antibody titers in Groups 2 and 3, there was enhanced protection in the younger animals in Group 3, against intravaginal infection with a heterologous SHIV strain. This protection correlated with the magnitude of the serum and vaginal Env-specific antibody titers on the day of challenge. Thus, vaccination strategies that induce both CD8+ T cell and antibody responses can confer enhanced protection against infection.