Cardiolipin polyspecific autoreactivity in two broadly neutralizing HIV-1 antibodies.
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.
Haynes
Barton F
BF
Duke University School of Medicine, Durham, NC 27710, USA. hayne002@mc.duke.edu
Fleming
Judith
J
St Clair
E William
EW
Katinger
Herman
H
Stiegler
Gabriela
G
Kunert
Renate
R
Robinson
James
J
Scearce
Richard M
RM
Plonk
Kelly
K
Staats
Herman F
HF
Ortel
Thomas L
TL
Liao
Hua-Xin
HX
Alam
S Munir
SM
D016915:AIDS Vaccines / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000737:chemistry / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000276:immunology; D002308:Cardiolipins / Q000276:immunology*; D045744:Cell Line, Tumor; D000939:Epitopes; D015483:HIV Antibodies / Q000737:chemistry / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D051379:Mice; D018716:Molecular Mimicry; D009500:Neutralization Tests
D016915:AIDS Vaccines; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens; D002308:Cardiolipins; D000939:Epitopes; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41