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Pathogenesis and Immunity

Broad Neutralization of Human Immunodeficiency Virus Type 1 Mediated by Plasma Antibodies against the gp41 Membrane Proximal External Region

Elin S. Gray, Maphuti C. Madiga, Penny L. Moore, Koleka Mlisana, Salim S. Abdool Karim, James M. Binley, George M. Shaw, John R. Mascola, Lynn Morris
Elin S. Gray
1AIDS Virus Research Unit, National Institute for Communicable Diseases, Johannesburg, South Africa
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Maphuti C. Madiga
1AIDS Virus Research Unit, National Institute for Communicable Diseases, Johannesburg, South Africa
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Penny L. Moore
1AIDS Virus Research Unit, National Institute for Communicable Diseases, Johannesburg, South Africa
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Koleka Mlisana
2Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu Natal, Durban, South Africa
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Salim S. Abdool Karim
2Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu Natal, Durban, South Africa
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James M. Binley
3Torrey Pines Institute for Molecular Studies, San Diego, California 92121
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George M. Shaw
4University of Alabama at Birmingham, Birmingham, Alabama 35294
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John R. Mascola
5Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892
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Lynn Morris
1AIDS Virus Research Unit, National Institute for Communicable Diseases, Johannesburg, South Africa
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  • For correspondence: lynnm@nicd.ac.za
DOI: 10.1128/JVI.01359-09
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ABSTRACT

We identified three cross-neutralizing plasma samples with high-titer anti-membrane proximal external region (MPER) peptide binding antibodies from among 156 chronically human immunodeficiency virus type 1-infected individuals. In order to establish if these antibodies were directly responsible for the observed neutralization breadth, we used MPER-coated magnetic beads to deplete plasmas of these specific antibodies. Depletion of anti-MPER antibodies from BB34, CAP206, and SAC21 resulted in 77%, 68%, and 46% decreases, respectively, in the number of viruses neutralized. Antibodies eluted from the beads showed neutralization profiles similar to those of the original plasmas, with potencies comparable to those of the known anti-MPER monoclonal antibodies (MAbs), 4E10, 2F5, and Z13e1. The anti-MPER neutralizing antibodies in BB34 were present in the immunoglobulin G3 subclass-enriched fraction. Alanine scanning of the MPER showed that the antibodies from these three plasmas had specificities distinct from those of the known MAbs, requiring one to three crucial residues at positions 670, 673, and 674. These data demonstrate the existence of MPER-specific cross-neutralizing antibodies in plasma, although the ability to elicit such potent antiviral antibodies during natural infection appears to be rare. Nevertheless, the identification of three novel antibody specificities within the MPER supports its further study as a promising target for vaccine design.

  • Copyright © 2009 American Society for Microbiology
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Broad Neutralization of Human Immunodeficiency Virus Type 1 Mediated by Plasma Antibodies against the gp41 Membrane Proximal External Region
Elin S. Gray, Maphuti C. Madiga, Penny L. Moore, Koleka Mlisana, Salim S. Abdool Karim, James M. Binley, George M. Shaw, John R. Mascola, Lynn Morris
Journal of Virology Oct 2009, 83 (21) 11265-11274; DOI: 10.1128/JVI.01359-09

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Broad Neutralization of Human Immunodeficiency Virus Type 1 Mediated by Plasma Antibodies against the gp41 Membrane Proximal External Region
Elin S. Gray, Maphuti C. Madiga, Penny L. Moore, Koleka Mlisana, Salim S. Abdool Karim, James M. Binley, George M. Shaw, John R. Mascola, Lynn Morris
Journal of Virology Oct 2009, 83 (21) 11265-11274; DOI: 10.1128/JVI.01359-09
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KEYWORDS

antibodies
HIV Envelope Protein gp41
HIV-1

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