Neutralization of HIV-1 by redirection of natural antibodies

@article{citeulike:3158001, abstract = {10.1073/pnas.0805777105 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 . 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.}, author = {Perdomo, Maria F. and Levi, Michael and S\"{a}llberg, Matti and Vahlne, Anders }, citeulike-article-id = {3158001}, doi = {http://dx.doi.org/10.1073/pnas.0805777105}, journal = {Proceedings of the National Academy of Sciences}, keywords = {hiv, neutralization}, number = {34}, pages = {12515--12520}, posted-at = {2008-08-27 10:09:48}, priority = {2}, title = {Neutralization of HIV-1 by redirection of natural antibodies}, url = {http://dx.doi.org/10.1073/pnas.0805777105}, volume = {105}, year = {2008} }

TY - JOUR ID - citeulike:3158001 L3 - citeulike-article-id:3158001 N2 - 10.1073/pnas.0805777105 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 . 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. IS - 34 JF - Proceedings of the National Academy of Sciences EP - 12520 TI - Neutralization of HIV-1 by redirection of natural antibodies VL - 105 SP - 12515 KW - hiv KW - neutralization AU - Perdomo, Maria AU - Levi, Michael AU - Sällberg, Matti AU - Vahlne, Anders PY - 2008//26/ UR - http://dx.doi.org/10.1073/pnas.0805777105 ER -