Neutralization of HIV-1 by redirection of natural antibodies
- *Division of Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital at Huddinge F-68, SE-141 86 Stockholm, Sweden; and
- †Tripep AB, Hälsovägen 7, SE-141 57 Huddinge, Sweden
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Communicated by Robert C. Gallo, University of Maryland, Baltimore, MD, June 15, 2008 (received for review February 15, 2008)
Abstract
The great variability and high glycosylation of gp120 poses a great challenge for the design of a functional immune therapy. The binding region of the CD4 receptor to gp120, however, is well conserved and may constitute a target to limit viral entry and infectivity. Our strategy consists in using a preexisting pool of natural antibodies directed toward the gal(α1,3)gal disaccharide and to redirect it to HIV. We here show that using CD4-derived, gp120-binding, synthetic peptides chemically linked to gal(α1,3)gal can redirect these natural antibodies and improve the HIV-1 neutralizing activity of the CD4-derived peptides in vitro. Importantly, the binding of the CD4-gal(α1,3)gal peptides to HIV-1–infected cells conferred antibody-dependent cellular cytotoxicity after the addition of human sera. Thus, the temporary redirection of naturally occurring antibodies and their biological activities to a new antigen represents a completely new way of targeting a human disease.
Footnotes
- ‡To whom correspondence should be addressed. E-mail:anders.vahlne{at}ki.se
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Author contributions: M.F.P., M.S., and A.V. designed research; M.F.P. and M.L. performed research; M.F.P., M.S., and A.V. analyzed data; and M.F.P., M.S., and A.V. wrote the paper.
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Conflict of interest statement: A.V. and M.S. own shares in Tripep AB, the company that holds the intellectual property. M.L. is an employee of Tripep AB
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Freely available online through the PNAS open access option.
- © 2008 by The National Academy of Sciences of the USA
