Protection of Humanized Mice From Repeated Intravaginal HIV Challenge by Passive Immunization: A Model for Studying the Efficacy of Neutralizing Antibodies In Vivo

Maud Deruaz; Brian Moldt; Khoa M Le; Karen A Power; Vladimir D Vrbanac; Serah Tanno; Musie S Ghebremichael; Todd M Allen; Andrew M Tager; Dennis R Burton; Andrew D Luster

doi:10.1093/infdis/jiw203

Protection of Humanized Mice From Repeated Intravaginal HIV Challenge by Passive Immunization: A Model for Studying the Efficacy of Neutralizing Antibodies In Vivo

J Infect Dis. 2016 Aug 15;214(4):612-6. doi: 10.1093/infdis/jiw203. Epub 2016 Jun 29.

Authors

Affiliations

¹ Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston.
² 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.
³ Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts.
⁴ 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.
⁵ 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.

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.

Keywords: HIV transmission; humanized mice; mucosal infection; neutralizing antibodies.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Neutralizing / administration & dosage*
Disease Models, Animal*
Dose-Response Relationship, Immunologic
Female
HIV Antibodies / administration & dosage*
HIV Infections / prevention & control*
Immunization, Passive / methods*
Mice
Mice, SCID
Treatment Outcome

Substances

Antibodies, Neutralizing
HIV Antibodies

Abstract

Publication types

MeSH terms

Substances

Grants and funding