CaltechAUTHORS
  A Caltech Library Service

Adaptation of HIV-1 Envelope Glycoprotein gp120 to Humoral Immunity over the Course of the Epidemic

Bouvin-Pley, Mélanie and Morgand, Marion and Moreau, Alain and Meyer, Laurence and Goujard, Cecile and Mouquet, Hugo and Nussenzweig, Michel C. and Pace, Craig S. and Ho, David D. and Bjorkman, Pamela J. and Baty, Daniel and Chames, Patrick and Pancera, Marie and Kwong, Peter D. and Poignard, Pascal and Barin, Francis and Braibant, Martine (2014) Adaptation of HIV-1 Envelope Glycoprotein gp120 to Humoral Immunity over the Course of the Epidemic. AIDS Research and Human Retroviruses, 30 (S1). A224. ISSN 0889-2229. https://resolver.caltech.edu/CaltechAUTHORS:20150211-074826079

[img] PDF - Published Version
See Usage Policy.

678Kb

Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20150211-074826079

Abstract

Since 2009, a large panel of broad and potent monoclonal neutralizing antibodies (MoNAbs) against HIV-1 have been isolated. These MoNAbs can protect from lllV-1 infection and suppress established infection in animal models. Because their efficacy should be evaluated in human clinical trials, it is of importance to define the sensitivity of the most contemporary transmitted variants to these MoNAbs. We, and others previously, reported that HIV-1 has become more resistant to neutralization over the course of the epidemic (Bunnik et al., Nature Med 2010, Bouvin-Pley et al., PloS Pathog 2013). Methods: Here we extended the analyses to the most potent MoNAbs described since then, either more recently isolated or improved by structure-based gene modifications. Results: We fully confirmed the first observations showing an increasing resistance of HIV-1 clade B over time to MoNAbs targeting the major gp l20 epitopes but not to MoNAbs targeting the gp41 MPER. Despite this evolution, some MoNAbs still were able to neutralize efficiently the most recently transmitted HIV-1 variants (2006-2010). The most potent MoNAbs were the bi-specific PG9- and PG16-iMab that alone were able to neutralize an variants at less than 0.4 mg/mL. The sensitivity to iMAb remained similar over time, suggesting that the trend of increasing resistance to PG9-/PG16-iMAb may be attributed only to die antigen binding domain of PG9/PG16. NIH45-46m2 (and -m7), 10-1074 and 10E8 were also highly potent and, if combined, reached the potency of PG9-/PG16-iMAb. We also observed that 3BNC 117 was almost as potent as the modified NIH45-46 antibodies, and that the lama-derived JM4IgG2b was the most potent Ab among those that do not target the major gp 120 neutralizing epitopes. Conclusions: These data clearly suggest a continuous drift of the env gene of HIV-1 elude B over the epidemic, and that not a single epitope is concerned but the entire gp120 as a whole. The consequences of this adaptation on the envelope functionality are being explored.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/doi:10.1089/aid.2014.5490.abstractDOIArticle
http://online.liebertpub.com/doi/abs/10.1089/aid.2014.5490.abstractPublisherArticle
ORCID:
AuthorORCID
Bouvin-Pley, Mélanie0000-0002-2480-931X
Nussenzweig, Michel C.0000-0003-0592-8564
Bjorkman, Pamela J.0000-0002-2277-3990
Additional Information:© 2014 Mary Ann Liebert, Inc. publishers.
Issue or Number:S1
Record Number:CaltechAUTHORS:20150211-074826079
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150211-074826079
Official Citation:Bouvin-Pley Melanie, Morgand Marion, Moreau Alain, Meyer Laurence, Goujard Cécile, Mouquet Hugo, Nussenzweig Michel C., Pace Craig S., Ho David D., Bjorkman Pamela J., Baty Daniel, Chames Patrick, Pancera Marie, Kwong Peter D., Poignard Pascal, Barin Francis, and Braibant Martine. AIDS Research and Human Retroviruses. October 2014, 30(S1): A224-A224. doi:10.1089/aid.2014.5490.abstract.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:54683
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:12 Feb 2015 00:50
Last Modified:03 Oct 2019 07:59

Repository Staff Only: item control page