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...
Autores principales: | , , , , , , , |
---|---|
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 |