Targeting alpha(4)beta(7) integrin reduces mucosal transmission of simian immunodeficiency virus and protects gut-associated lymphoid tissue from infection

• Type of Material: Article
• Authors: Siddappa Byrareddy, Emory University; Brianne Kallam, Emory University; James Arthos, National Institute of Allergy & Infectious Diseases; Claudia Cicala, National Institute of Allergy & Infectious Diseases; Fatima Nawaz, National Institute of Allergy & Infectious Diseases; Joseph Hiatt, National Institute of Allergy & Infectious Diseases; Ellen N. Kersh, Centers for Disease Control and Prevention; Janet M. McNicholl, Centers for Disease Control and Prevention; Debra Hanson, Centers for Disease Control and Prevention; Keith A. Reimann, University of Massachusetts; Markus Brameier, German Primate Center; Lutz Walter, German Primate Center; Kael Rogers, Emory University; Ann E. Mayne, Emory University; Paul Dunbar, Emory University; Tara Villinger, Emory University; Dawn Little, Emory University; Tristram Parslow, Emory University; Philip Santangelo, Emory University; Francois Villinger, Emory University; Anthony S. Fauci, National Institute of Allergy & Infectious Diseases; Aftab Ansari, Emory University
• Language: English
• Date: 2014-12-01
• Publisher: Nature Research (part of Springer Nature)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014 Nature America, Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/nm.3715
• Title of Journal or Parent Work: Nature Medicine
• ISSN: 1078-8956
• Volume: 20
• Issue: 12
• Start Page: 1397
• End Page: 1400
• Grant/Funding Information: This work was supported by a grant from the NIH-NIAID AI-098628-01 (AAA) and OD 51POD1113 to the Yerkes National Primate Research Center.; Recombinant monoclonal antibodies were produced by the Nonhuman Primate Reagent Resource (NIAID, NIH contract # HHSN272200900037C).
• Keywords: VEDOLIZUMAB; CD4; Cell Biology; INDUCTION; RECEPTOR; MAINTENANCE THERAPY; Life Sciences & Biomedicine; T-CELL SUBSET; Biochemistry & Molecular Biology; IMMUNE ACTIVATION; Research & Experimental Medicine; Medicine, Research & Experimental; TRACT; Science & Technology; DEPLETION; ALPHA-4-BETA-7
• Research Categories: Health Sciences, Pathology; Health Sciences, Immunology; Biology, Microbiology

Abstract

α4β7 integrin-expressing CD4+ T cells preferentially traffic to gut-associated lymphoid tissue (GALT) and have a key role in HIV and simian immunodeficiency virus (SIV) pathogenesis. We show here that the administration of an anti-α4β7 monoclonal antibody just prior to and during acute infection protects rhesus macaques from transmission following repeated low-dose intravaginal challenges with SIV mac251. In treated animals that became infected, the GALT was significantly protected from infection and CD4+ T cell numbers were maintained in both the blood and the GALT. Thus, targeting α4β7 reduces mucosal transmission of SIV in macaques.