期刊论文详细信息
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
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【 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   

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