title: Targeting α4β7 integrin reduces mucosal transmission of simian immunodeficiency virus and protects gut-associated lymphoid tissue from infection.
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 SIVmac251. 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Siddappa N
authors.initials: SN
authors.lastname: Byrareddy
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Brianne
authors.initials: B
authors.lastname: Kallam
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy &Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors.forename: James
authors.initials: J
authors.lastname: Arthos
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy &Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cicala
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy &Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors.forename: Fatima
authors.initials: F
authors.lastname: Nawaz
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy &Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Hiatt
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Ellen N
authors.initials: EN
authors.lastname: Kersh
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Janet M
authors.initials: JM
authors.lastname: McNicholl
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
authors.forename: Debra
authors.initials: D
authors.lastname: Hanson
authors.affiliation: Mass Biologics, University of Massachusetts Medical School, Boston, Massachusetts, USA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Reimann
authors.affiliation: Primate Genetics Laboratory, German Primate Center, Leibniz-Institute for Primate Research, Göttingen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Brameier
authors.affiliation: Primate Genetics Laboratory, German Primate Center, Leibniz-Institute for Primate Research, Göttingen, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Walter
authors.affiliation: Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Rogers
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Ann E
authors.initials: AE
authors.lastname: Mayne
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Dunbar
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Tara
authors.initials: T
authors.lastname: Villinger
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Dawn
authors.initials: D
authors.lastname: Little
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Tristram G
authors.initials: TG
authors.lastname: Parslow
authors.affiliation: Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, Georgia, USA.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Santangelo
authors.affiliation: 1] Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA. [2] Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
authors.forename: Francois
authors.initials: F
authors.lastname: Villinger
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy &Infectious Diseases, National Institutes of Health (NIH), Bethesda, Maryland, USA.
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Fauci
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Aftab A
authors.initials: AA
authors.lastname: Ansari
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002584:Cervix Uteri / Q000821:virology; D003106:Colon / Q000821:virology; D004279:DNA, Viral / Q000032:analysis*; D005260:Female; D007082:Ileum / Q000821:virology; D016023:Integrins / Q000037:antagonists & inhibitors* / Q000276:immunology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology; D007583:Jejunum / Q000821:virology; D008221:Lymphoid Tissue / Q000187:drug effects* / Q000276:immunology; D008253:Macaca mulatta; D009092:Mucous Membrane / Q000187:drug effects / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000635:transmission*; D015302:Simian Immunodeficiency Virus / Q000235:genetics; D014621:Vagina / Q000187:drug effects* / Q000276:immunology; D019562:Viral Load
chemical_list: D000911:Antibodies, Monoclonal; D004279:DNA, Viral; D016023:Integrins; C071777:integrin alpha4beta7