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PLoS Pathog. 2010 Dec 16;6(12):e1001225. doi: 10.1371/journal.ppat.1001225.

Dimeric 2G12 as a potent protection against HIV-1.

Author information

1
Division of Biology, California Institute of Technology, Pasadena, California, United States of America.

Abstract

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.

PMID:
21187894
PMCID:
PMC3002980
DOI:
10.1371/journal.ppat.1001225
[Indexed for MEDLINE]
Free PMC Article

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