Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Luo, Xin M., Lei, Margarida Y. Y., Feidi, Rana A., West, Anthony P., Balazs, Alejandro Benjamin, Bjorkman, Pamela J., Yang, Lili, Baltimore, David
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002980/
https://www.ncbi.nlm.nih.gov/pubmed/21187894
http://dx.doi.org/10.1371/journal.ppat.1001225
_version_ 1782193819040612352
author Luo, Xin M.
Lei, Margarida Y. Y.
Feidi, Rana A.
West, Anthony P.
Balazs, Alejandro Benjamin
Bjorkman, Pamela J.
Yang, Lili
Baltimore, David
author_facet Luo, Xin M.
Lei, Margarida Y. Y.
Feidi, Rana A.
West, Anthony P.
Balazs, Alejandro Benjamin
Bjorkman, Pamela J.
Yang, Lili
Baltimore, David
author_sort Luo, Xin M.
collection PubMed
description 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.
format Text
id pubmed-3002980
institution National Center for Biotechnology Information
language English
publishDate 2010
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-30029802010-12-27 Dimeric 2G12 as a Potent Protection against HIV-1 Luo, Xin M. Lei, Margarida Y. Y. Feidi, Rana A. West, Anthony P. Balazs, Alejandro Benjamin Bjorkman, Pamela J. Yang, Lili Baltimore, David PLoS Pathog Research Article 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. Public Library of Science 2010-12-16 /pmc/articles/PMC3002980/ /pubmed/21187894 http://dx.doi.org/10.1371/journal.ppat.1001225 Text en Luo et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Luo, Xin M.
Lei, Margarida Y. Y.
Feidi, Rana A.
West, Anthony P.
Balazs, Alejandro Benjamin
Bjorkman, Pamela J.
Yang, Lili
Baltimore, David
Dimeric 2G12 as a Potent Protection against HIV-1
title Dimeric 2G12 as a Potent Protection against HIV-1
title_full Dimeric 2G12 as a Potent Protection against HIV-1
title_fullStr Dimeric 2G12 as a Potent Protection against HIV-1
title_full_unstemmed Dimeric 2G12 as a Potent Protection against HIV-1
title_short Dimeric 2G12 as a Potent Protection against HIV-1
title_sort dimeric 2g12 as a potent protection against hiv-1
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002980/
https://www.ncbi.nlm.nih.gov/pubmed/21187894
http://dx.doi.org/10.1371/journal.ppat.1001225
work_keys_str_mv AT luoxinm dimeric2g12asapotentprotectionagainsthiv1
AT leimargaridayy dimeric2g12asapotentprotectionagainsthiv1
AT feidiranaa dimeric2g12asapotentprotectionagainsthiv1
AT westanthonyp dimeric2g12asapotentprotectionagainsthiv1
AT balazsalejandrobenjamin dimeric2g12asapotentprotectionagainsthiv1
AT bjorkmanpamelaj dimeric2g12asapotentprotectionagainsthiv1
AT yanglili dimeric2g12asapotentprotectionagainsthiv1
AT baltimoredavid dimeric2g12asapotentprotectionagainsthiv1