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Journal of Virology, September 2009, p. 8925-8937, Vol. 83, No. 17
0022-538X/09/$08.00+0     doi:10.1128/JVI.00758-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Antibody Specificities Associated with Neutralization Breadth in Plasma from Human Immunodeficiency Virus Type 1 Subtype C-Infected Blood Donors{triangledown} ,{dagger}

Elin S. Gray,1 Natasha Taylor,1 Diane Wycuff,3 Penny L. Moore,1 Georgia D. Tomaras,4 Constantinos Kurt Wibmer,1 Adrian Puren,2 Allan DeCamp,5 Peter B. Gilbert,5 Blake Wood,5 David C. Montefiori,4 James M. Binley,6 George M. Shaw,7 Barton F. Haynes,4 John R. Mascola,3 and Lynn Morris1*

AIDS Virus Research Unit,1 Specialized Molecular Diagnostics Unit, National Institute for Communicable Diseases, Johannesburg 2193, South Africa,2 Vaccine Research Centre, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892,3 Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina 27710,4 Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109,5 Torrey Pines Institute for Molecular Studies, San Diego, California 92121,6 University of Alabama at Birmingham, Birmingham, Alabama 352947

Received 14 April 2009/ Accepted 13 June 2009

Defining the specificities of the anti-human immunodeficiency virus type 1 (HIV-1) envelope antibodies able to mediate broad heterologous neutralization will assist in identifying targets for an HIV-1 vaccine. We screened 70 plasmas from chronically HIV-1-infected individuals for neutralization breadth. Of these, 16 (23%) were found to neutralize 80% or more of the viruses tested. Anti-CD4 binding site (CD4bs) antibodies were found in almost all plasmas independent of their neutralization breadth, but they mainly mediated neutralization of the laboratory strain HxB2 with little effect on the primary virus, Du151. Adsorption with Du151 monomeric gp120 reduced neutralizing activity to some extent in most plasma samples when tested against the matched virus, although these antibodies did not always confer cross-neutralization. For one plasma, this activity was mapped to a site overlapping the CD4-induced (CD4i) epitope and CD4bs. Anti-membrane-proximal external region (MPER) (r = 0.69; P < 0.001) and anti-CD4i (r = 0.49; P < 0.001) antibody titers were found to be correlated with the neutralization breadth. These anti-MPER antibodies were not 4E10- or 2F5-like but spanned the 4E10 epitope. Furthermore, we found that anti-cardiolipin antibodies were correlated with the neutralization breadth (r = 0.67; P < 0.001) and anti-MPER antibodies (r = 0.6; P < 0.001). Our study suggests that more than one epitope on the envelope glycoprotein is involved in the cross-reactive neutralization elicited during natural HIV-1 infection, many of which are yet to be determined, and that polyreactive antibodies are possibly involved in this phenomenon.

* Corresponding author. Mailing address: National Institute for Communicable Diseases, Johannesburg, Private Bag X4, Sandringham 2131, Johannesburg, South Africa. Phone: 27-11-386-6332. Fax: 27-11-386-6333. E-mail: lynnm{at}nicd.ac.za

{triangledown} Published ahead of print on 24 June 2009.

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

Journal of Virology, September 2009, p. 8925-8937, Vol. 83, No. 17
0022-538X/09/$08.00+0     doi:10.1128/JVI.00758-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



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