JVI Accepts, published online ahead of print on 24 June 2009

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J. Virol. doi:10.1128/JVI.00758-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Antibody specificities associated with neutralization breadth in plasma from HIV-1 subtype C infected blood donors

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

AIDS Virus Research Unit and Specialized Molecular Diagnostics Unit, National Institute for Communicable Diseases, Johannesburg 2193, South Africa; Vaccine Research Centre, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA; Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Torrey Pines Institute for Molecular Studies, San Diego, CA 92121, USA; University of Alabama at Birmingham, Birmingham, AL 35294, USA

^* To whom correspondence should be addressed. Email: lynnm{at}nicd.ac.za.

Defining the specificities of the anti-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 HIV-1 chronically infected individuals for neutralization breadth. Of these, 16 (23%) were found to neutralize 80% or more of the viruses tested. Anti-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 over 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 CD4i epitope and CD4bs. Anti-MPER (r=0.69, P<0.001) and anti-CD4i (r=0.49, P<0.001) antibody titers were found to correlate with neutralization breadth. These anti-MPER antibodies were not 4E10 or 2F5-like but spanned the 4E10 epitope. Furthermore, we found anti-cardiolipin antibodies correlated with 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 HIV-1 natural infection, many of which are yet to be determined, and the possible involvement of polyreactive antibodies in this phenomenon.

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