title: Protection of Humanized Mice From Repeated Intravaginal HIV Challenge by Passive Immunization: A Model for Studying the Efficacy of Neutralizing Antibodies In Vivo.
abstract: Humanized mice reconstituted with a human immune system can be mucosally infected with human immunodeficiency virus (HIV), opening up the possibility of studying HIV transmission in a small-animal model. Here we report that passive immunization with the broadly neutralizing antibody b12 protected humanized mice against repetitive intravaginal infection in a dose-dependent manner. In addition, treatment with the antibody PGT126, which is more potent in vitro, was more efficacious in vivo and provided sterilizing protection. Our results demonstrate that humanized mice can be used as a small-animal model to study the efficacy and mechanism of broadly neutralizing antibody protection against HIV acquisition.
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston.
authors.forename: Maud
authors.initials: M
authors.lastname: Deruaz
authors.affiliation: Department of Immunology and Microbial Science, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, and IAVI Neutralizing Antibody Center, Scripps Research Institute, La Jolla, California.
authors.forename: Brian
authors.initials: B
authors.lastname: Moldt
authors.affiliation: Department of Immunology and Microbial Science, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, and IAVI Neutralizing Antibody Center, Scripps Research Institute, La Jolla, California.
authors.forename: Khoa M
authors.initials: KM
authors.lastname: Le
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Power
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts.
authors.forename: Vladimir D
authors.initials: VD
authors.lastname: Vrbanac
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts.
authors.forename: Serah
authors.initials: S
authors.lastname: Tanno
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts.
authors.forename: Musie S
authors.initials: MS
authors.lastname: Ghebremichael
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts.
authors.forename: Todd M
authors.initials: TM
authors.lastname: Allen
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Tager
authors.affiliation: Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts Department of Immunology and Microbial Science, Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, and IAVI Neutralizing Antibody Center, Scripps Research Institute, La Jolla, California.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.affiliation: Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Luster
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D015483:HIV Antibodies / Q000008:administration & dosage*; D015658:HIV Infections / Q000517:prevention & control*; D007116:Immunization, Passive / Q000379:methods*; D051379:Mice; D016513:Mice, SCID; D016896:Treatment Outcome
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies
keywords: HIV transmission; humanized mice; mucosal infection; neutralizing antibodies