Neutralization of HIV-1 by redirection of natural antibodies.

Proceedings of the National Academy of Sciences of the United States of America
Maria F PerdomoAnders Vahlne

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(alpha1,3)gal disaccharide and to redirect it to HIV. We here show that using CD4-derived, gp120-binding, synthetic peptides chemically linked to gal(alpha1,3)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(alpha1,3)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.

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Citations

Aug 24, 2010·Journal of the American Chemical Society·Andrew X ZhangDavid A Spiegel
Nov 6, 2009·Journal of the American Chemical Society·Ryan P MurelliDavid A Spiegel
Oct 11, 2012·Proceedings of the National Academy of Sciences of the United States of America·Maria F PerdomoAnders Vahlne
May 9, 2012·AIDS Research and Human Retroviruses·Maria F PerdomoAnders Vahlne
Apr 4, 2016·Current Allergy and Asthma Reports·Scott P ComminsMike Kulis
May 6, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hualin LiCatarina E Hioe
Jun 5, 2020·Chembiochem : a European Journal of Chemical Biology·Annemiek Uvyn, Bruno G De Geest
Aug 25, 2020·Journal of Medical Virology·Ji-Ming Chen
Oct 16, 2019·Chemistry : a European Journal·Benjamin LietOlivier Renaudet
Oct 21, 2009·Journal of the American Chemical Society·Christopher G ParkerDavid A Spiegel
Sep 24, 2013·ACS Chemical Biology·Charles E JakobscheDavid A Spiegel
May 25, 2018·ACS Chemical Biology·Shanshan LiBinghe Wang

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