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Published Online April 28, 2005
Science DOI: 10.1126/science.1111781

Reports

Submitted on March 3, 2005
Accepted on April 19, 2005

Cardiolipin Polyspecific Autoreactivity in Two Broadly Neutralizing HIV-1 Antibodies

Barton F. Haynes 1*, Judith Fleming 1, William E. 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, Munir S. Alam 1

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.
Barton F. Haynes , E-mail: hayne002{at}mc.duke.edu

Design of an HIV-1 immunogen that can induce broadly reactive neutralizing antibodies is a major goal of HIV-1 vaccine development. Although rare human MAbs exist that broadly neutralize HIV-1, HIV-1 envelope immunogens do not induce these antibody specificities. In this study, 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 using HIV-1 vaccines.


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