Neutralization of HIV-1 by redirection of natural antibodies.
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.
Perdomo
Maria F
MF
Division of Clinical Microbiology, Karolinska Institutet, Karolinska University Hospital at Huddinge F-68, SE-141 86 Stockholm, Sweden.
Levi
Michael
M
Sällberg
Matti
M
Vahlne
Anders
A
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000906:Antibodies / Q000737:chemistry / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity; D015704:CD4 Antigens / Q000737:chemistry / Q000276:immunology; D004187:Disaccharides / Q000737:chemistry / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D018716:Molecular Mimicry; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology / Q000627:therapeutic use; D011991:Receptors, Virus
D019380:Anti-HIV Agents; D000906:Antibodies; D015704:CD4 Antigens; D004187:Disaccharides; D015699:HIV Envelope Protein gp120; D010446:Peptide Fragments; D011991:Receptors, Virus; C055075:galactosyl-(1-3)galactose