Dimeric 2G12 as a potent protection against HIV-1

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 aga...

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Bibliographic Details
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
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Summary: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.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1001225