Drift of the HIV-1 envelope glycoprotein gp120 toward increased neutralization resistance over the course of the epidemic: a comprehensive study using the most potent and broadly neutralizing monoclonal antibodies

M Bouvin-Pley; M Morgand; L Meyer; C Goujard; A Moreau; H Mouquet; M Nussenzweig; C Pace; D Ho; P J Bjorkman; D Baty; P Chames; M Pancera; P D Kwong; P Poignard; F Barin; M Braibant

doi:10.1128/JVI.02083-14

Drift of the HIV-1 envelope glycoprotein gp120 toward increased neutralization resistance over the course of the epidemic: a comprehensive study using the most potent and broadly neutralizing monoclonal antibodies

J Virol. 2014 Dec;88(23):13910-7. doi: 10.1128/JVI.02083-14. Epub 2014 Sep 17.

Authors

M Bouvin-Pley¹, M Morgand¹, L Meyer², C Goujard², A Moreau¹, H Mouquet³, M Nussenzweig⁴, C Pace⁵, D Ho⁵, P J Bjorkman⁶, D Baty⁷, P Chames⁷, M Pancera⁸, P D Kwong⁸, P Poignard⁹, F Barin¹⁰, M Braibant¹¹

Affiliations

¹ Université François Rabelais, Inserm U966, Tours, France.
² Université Paris Sud, CESP Inserm U1018, Paris, France AP-HP Hôpital de Bicêtre, Le Kremlin-Bicêtre, France.
³ Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, Paris, France.
⁴ Howard Hughes Medical Institute, The Rockefeller University, New York, New York, USA.
⁵ Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York, USA.
⁶ California Institute of Technology, Pasadena, California, USA.
⁷ CRCM, Inserm U1068, Institut Paoli-Calmettes, CNRS UMR7258, Marseille, France.
⁸ Vaccine Research Center, National Institutes of Health, Bethesda, Maryland, USA.
⁹ Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, California, USA International AIDS Vaccine Initiative Neutralizing Antibody Center, La Jolla, California, USA.
¹⁰ Université François Rabelais, Inserm U966, Tours, France Laboratoire de Bactériologie-Virologie and Centre National de Reference du VIH, CHU Bretonneau, Tours, France.
¹¹ Université François Rabelais, Inserm U966, Tours, France braibant@med.univ-tours.fr.

Abstract

Extending our previous analyses to the most recently described monoclonal broadly neutralizing antibodies (bNAbs), we confirmed a drift of HIV-1 clade B variants over 2 decades toward higher resistance to bNAbs targeting almost all the identified gp120-neutralizing epitopes. In contrast, the sensitivity to bNAbs targeting the gp41 membrane-proximal external region remained stable, suggesting a selective pressure on gp120 preferentially. Despite this evolution, selected combinations of bNAbs remain capable of neutralizing efficiently most of the circulating variants.

Publication types

Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Monoclonal / immunology*
Antibodies, Neutralizing / immunology*
Epidemics
Genetic Drift*
HIV Antibodies / immunology*
HIV Envelope Protein gp120 / genetics
HIV Envelope Protein gp120 / immunology*
HIV Envelope Protein gp41 / genetics
HIV Envelope Protein gp41 / immunology
HIV Infections / epidemiology
HIV Infections / immunology*
HIV Infections / virology
HIV-1 / genetics
HIV-1 / immunology*
HIV-1 / isolation & purification
Humans
Male
Mice
Neutralization Tests

Substances

Antibodies, Monoclonal
Antibodies, Neutralizing
HIV Antibodies
HIV Envelope Protein gp120
HIV Envelope Protein gp41
gp120 protein, Human immunodeficiency virus 1
gp41 protein, Human immunodeficiency virus 1

Abstract

Publication types

MeSH terms

Substances

Grants and funding