T cell-inducing vaccine durably prevents mucosal SHIV infection even with lower neutralizing antibody titers

• Type of Material: Article
• Authors: Prabhu S. Arunachalam, Stanford University; Tysheena P. Charles, Yerkes National Primate Research Center; Vineet Joag, University of Minnesota; Venkata S. Bollimpelli, Emory University; Madeleine K. D. Scott, Stanford University; Florian Wimmers, Stanford University; Samantha L. Burton, Yerkes National Primate Research Center; Celia C. Labranche, Duke University; Caroline Petitdemange, Emory University; Sailaja Gangadhara, Emory University; Tiffany M. Styles, Emory University; Clare F. Quarnstrom, University of Minnesota; Korey A. Walter, Louisiana State University; Thomas J. Ketas, Cornell University; Traci Legere, Emory University; PBJ Reddy, Emory University; Sudhir Kasturi, Emory University; Anthony Tsai, BioLegend; Bertrand Z. Yeung, BioLegend; Shakti Gupta, University of California San Diego; Mark Tomai, 3M Corporate Research and Materials Lab; John Vasilakos, 3M Drug Delivery Systems; George M. Shaw, University of Pennsylvania; Chil Yong Kang, University of Western Ontario; John P. Moore, Cornell University; Shankar Subramaniam, University of California San Diego; Purvesh Khatri, Stanford University; David Montefiori, Duke University; Pamela A. Kozlowski, Louisiana State University; Cynthia Derdeyn, Emory University; Eric Hunter, Emory University; David Masopust, University of Minnesota; Rama Amara, Emory University; Bali Pulendran, Emory University
• Language: English
• Date: 2020-06-01
• Publisher: Nature Publishing Group
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2020.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41591-020-0858-8
• Title of Journal or Parent Work: Nature Medicine
• Volume: 26
• Issue: 6
• Start Page: 932
• End Page: +
• Grant/Funding Information: This project was funded in part by the Yerkes National Primate Research Center Grant No. ORIP/OD P51OD011132, supported by the NIH, Office of Research Infrastructure Programs.; This work was supported by NIH grants UM1 AI124436 (Emory Consortium for Innovative AIDS Research in Nonhuman Primates, Principal Investigators E.H. and R.R.A.), NIAID UM1AI100663 (Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery to B.P. (Principal Investigator of the program, D. Burton) and the Bill and Melinda Gates Foundation Center for AIDS Vaccine Discovery (to B.P.) and HIVRAD P01 AI 110657 (to J.P.M.).
• Keywords: SIV; Cell Biology; Resistance; Research & Experimental Medicine; HIV-1 Infection; Responses; Acquisition; Life Sciences & Biomedicine; Science & Technology; AIDS; Expression; Biochemistry & Molecular Biology; Immunization; Envelope; Replication; Medicine, Research & Experimental
• Research Categories: Biology, Cell; Chemistry, Biochemistry; Health Sciences, Immunology; Biology, Molecular

Abstract

Recent efforts toward an HIV vaccine focus on inducing broadly neutralizing antibodies, but eliciting both neutralizing antibodies (nAbs) and cellular responses may be superior. Here, we immunized macaques with an HIV envelope trimer, either alone to induce nAbs, or together with a heterologous viral vector regimen to elicit nAbs and cellular immunity, including CD8+ tissue-resident memory T cells. After ten vaginal challenges with autologous virus, protection was observed in both vaccine groups at 53.3% and 66.7%, respectively. A nAb titer >300 was generally associated with protection but in the heterologous viral vector + nAb group, titers <300 were sufficient. In this group, protection was durable as the animals resisted six more challenges 5 months later. Antigen stimulation of T cells in ex vivo vaginal tissue cultures triggered antiviral responses in myeloid and CD4+ T cells. We propose that cellular immune responses reduce the threshold of nAbs required to confer superior and durable protection.