PLoS Pathogens | |
Dimeric 2G12 as a Potent Protection against HIV-1 | |
Anthony P. West Jr1  Alejandro Benjamin Balazs1  Lili Yang1  Rana A. Feidi1  Margarida Y. Y. Lei1  David Baltimore1  Pamela J. Bjorkman1  Xin M. Luo1  | |
[1] Division of Biology, California Institute of Technology, Pasadena, California, United States of America | |
关键词: HIV-1; Dimers (Chemical physics); Mouse models; Antibodies; Blood plasma; Viral load; Enzyme-linked immunoassays; T helper cells; | |
DOI : 10.1371/journal.ppat.1001225 | |
学科分类:生物科学(综合) | |
来源: Public Library of Science | |
【 摘 要 】
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.
【 授权许可】
CC BY
【 预 览 】
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