Cardiolipin polyspecific autoreactivity in two broadly neutralizing HIV-1 antibodies

BF Haynes, J Fleming, EW St. Clair, H Katinger… - Science, 2005 - science.org
BF Haynes, J Fleming, EW St. Clair, H Katinger, G Stiegler, R Kunert, J Robinson
Science, 2005science.org
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 …
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.
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