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Journal of Virology, November 2009, p. 11265-11274, Vol. 83, No. 21
0022-538X/09/$08.00+0     doi:10.1128/JVI.01359-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Broad Neutralization of Human Immunodeficiency Virus Type 1 Mediated by Plasma Antibodies against the gp41 Membrane Proximal External Region {triangledown} ,{dagger}

Elin S. Gray,1 Maphuti C. Madiga,1 Penny L. Moore,1 Koleka Mlisana,2 Salim S. Abdool Karim,2 James M. Binley,3 George M. Shaw,4 John R. Mascola,5 and Lynn Morris1*

AIDS Virus Research Unit, National Institute for Communicable Diseases, Johannesburg, South Africa,1 Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu Natal, Durban, South Africa,2 Torrey Pines Institute for Molecular Studies, San Diego, California 92121,3 University of Alabama at Birmingham, Birmingham, Alabama 35294,4 Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 208925

Received 2 July 2009/ Accepted 6 August 2009

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.

* Corresponding author. Mailing address: National Institute for Communicable Diseases, Johannesburg, Private Bag X4, Sandringham 2131, Johannesburg, South Africa. Phone: 2711-386-6332. Fax: 2711-386-6453. E-mail: lynnm{at}nicd.ac.za

{triangledown} Published ahead of print on 19 August 2009.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, November 2009, p. 11265-11274, Vol. 83, No. 21
0022-538X/09/$08.00+0     doi:10.1128/JVI.01359-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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