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Originally published in Science Express on 28 April 2005
Science 24 June 2005:
Vol. 308. no. 5730, pp. 1906 - 1908
DOI: 10.1126/science.1111781
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Reports

Cardiolipin Polyspecific Autoreactivity in Two Broadly Neutralizing HIV-1 Antibodies

Barton F. Haynes,1* Judith Fleming,1 E. William St. Clair,1 Herman Katinger,2 Gabriela Stiegler,2 Renate Kunert,2 James Robinson,3 Richard M. Scearce,1 Kelly Plonk,1 Herman F. Staats,1 Thomas L. Ortel,1 Hua-Xin Liao,1 S. Munir Alam1

The design of a human immunodeficiency virus–1 (HIV-1) immunogen that can induce broadly reactive neutralizing antibodies is a major goal of HIV-1 vaccine development. Although rare human monoclonal antibodies (mAbs) exist that broadly neutralize HIV-1, HIV-1 envelope immunogens do not induce these antibody specificities. Here we demonstrate that the two most broadly reactive HIV-1 envelope gp41 human mAbs, 2F5 and 4E10, are polyspecific autoantibodies reactive with the phospholipid cardiolipin. Thus, current HIV-1 vaccines may not induce these types of antibodies because of autoantigen mimicry of the conserved membrane-proximal epitopes of the virus. These results may have important implications for generating effective neutralizing antibody responses by using HIV-1 vaccines.

1 Duke University School of Medicine, Durham, NC 27710, USA.
2 Institute of Applied Microbiology, University of Agriculture, Vienna, Austria.
3 Tulane University School of Medicine, New Orleans, LA 70112, USA.

* To whom correspondence should be addressed. E-mail: hayne002{at}mc.duke.edu

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