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Dimeric 2G12 as a Potent Protection against HIV-1

Luo, Xin M. and Lei, Margarida Y. Y. and Feidi, Rana A. and West, Anthony P., Jr. and Balazs, Alejandro Benjamin and Bjorkman, Pamela J. and Yang, Lili and Baltimore, David (2010) Dimeric 2G12 as a Potent Protection against HIV-1. PLoS Pathogens, 6 (12). Art. No. e1001225. ISSN 1553-7366. PMCID PMC3002980. https://resolver.caltech.edu/CaltechAUTHORS:20110307-113044022

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1371/journal.ppat.1001225 DOIArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3002980/PublisherArticle
ORCID:
AuthorORCID
Bjorkman, Pamela J.0000-0002-2277-3990
Baltimore, David0000-0001-8723-8190
Additional Information:© 2010 Luo et al. 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 credited. Received August 10, 2010; Accepted November 10, 2010; Published December 16, 2010. Editor: Ronald C. Desrosiers, Harvard University, United States of America. This work was supported by the Bill and Melinda Gates Foundation through the Grand Challenges in Global Health Initiative (D.B.). The funder’s website is http://www.grandchallenges.org/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Christopher Foglesong (Protein Expression Center, California Institute of Technology) and Rachel Galimidi (California Institute of Technology) for expressing and purifying 2G12 monomer and dimer, Dr. Dong-Sung An (University of California, Los Angeles) for providing the reagents required for the establishment of the in-house HIV-1 viral load assay, Dr. Dinesh Rao (University of California, Los Angeles) for establishing contact with the UCLA immunohistochemistry facility, and Dr. Alex Sigal (California Institute of Technology) for suggestions about mathematical calculations. Author Contributions: Conceived and designed the experiments: XML LY DB. Performed the experiments: XML MYYL RAF. Analyzed the data: XML PJB LY DB. Contributed reagents/materials/analysis tools: XML APW ABB. Wrote the paper: XML APW PJB LY DB.
Funders:
Funding AgencyGrant Number
Bill and Melinda Gates FoundationUNSPECIFIED
Issue or Number:12
PubMed Central ID:PMC3002980
Record Number:CaltechAUTHORS:20110307-113044022
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20110307-113044022
Official Citation:Luo XM, Lei MYY, Feidi RA, West AP Jr, Balazs AB, et al. (2010) Dimeric 2G12 as a Potent Protection against HIV-1. PLoS Pathog 6(12): e1001225. doi:10.1371/journal.ppat.1001225
Usage Policy: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 credited.
ID Code:22695
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:08 Mar 2011 18:28
Last Modified:12 Feb 2020 20:08

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