Dimeric 2G12 as a potent protection against HIV-1

• Published in: PLoS pathogens 2010-12, Vol.6 (12), p.e1001225-e1001225
• Main Authors: Luo, Xin M, Lei, Margarida Y Y, Feidi, Rana A, West, Jr, Anthony P, Balazs, Alejandro Benjamin, Bjorkman, Pamela J, Yang, Lili, Baltimore, David
• Format: Article
• Language: English
• Subjects: AIDS vaccines; AIDS Vaccines - immunology; AIDS Vaccines - therapeutic use; Animals; CD4-Positive T-Lymphocytes; HIV; HIV Antibodies - immunology; HIV Antibodies - therapeutic use; HIV infection; HIV Infections - prevention & control; HIV-1 - immunology; Human immunodeficiency virus; Humans; Identification and classification; Immunoglobulin G; Immunology/Immunity to Infections; Infections; Infectious Diseases/HIV Infection and AIDS; Lymphocyte Count; Mice; Mice, Transgenic; Monoclonal antibodies; Physiological aspects; Prevention; Protein Multimerization; Studies; Treatment Outcome; Viral Load
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1001225

We previously showed that broadly neutralizing anti-HIV-1 antibody 2G12 (human IgG1) naturally forms dimers that are more potent than monomeric 2G12 in in vitro neutralization of various strains of HIV-1. In this study, we have investigated the protective effects of monomeric versus dimeric 2G12 against HIV-1 infection in vivo using a humanized mouse model. Our results showed that passively transferred, purified 2G12 dimer is more potent than 2G12 monomer at preventing CD4 T cell loss and suppressing the increase of viral load following HIV-1 infection of humanized mice. Using humanized mice bearing IgG "backpack" tumors that provided 2G12 antibodies continuously, we found that a sustained dimer concentration of 5-25 µg/ml during the course of infection provides effective protection against HIV-1. Importantly, 2G12 dimer at this concentration does not favor mutations of the HIV-1 envelope that would cause the virus to completely escape 2G12 neutralization. We have therefore identified dimeric 2G12 as a potent prophylactic reagent against HIV-1 in vivo, which could be used as part of an antibody cocktail to prevent HIV-1 infection.