Secondary Logo

Journal Logo

164 Using Epitopes Recognized by Monoclonal Antibodies as Vaccine Templates

Zolla-Pazner, Susan

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2011 - Volume 56 - Issue - p 69
doi: 10.1097/01.qai.0000397351.15427.4e

NYU School of Medicine, New York, NY

Bioinformatics analysis of gp120 sequence data demonstrates structural conservation in the 2nd and 3rd sequence-variable loops (V2 and V3) of gp120. Immunochemical data provide evidence of antigenic conservation in V2 and V3. Immunochemical and functional studies of monoclonal antibodies (mAbs) that target quaternary neutralizing epitopes (QNEs) composed of regions of V2 and V3 also provide evidence of cross-reactivity reflective of structural and antigenic conservation in this compound epitope. Since antibodies to these regions can mediate virus neutralization, these regions of the HIV-1 envelope should be included among the targets of an AIDS vaccine intended to induce neutralizing antibodies. In order to design immunogens that target structurally-conserved, sequence-variable regions of a protein, 3D visualization is required; this can be accomplished through physical methods (crystallography and NMR) and through molecular modeling. Indeed, these approaches have revealed generic structures for the V3 loop and suggest related structures recognized by macaque and human QNE mAbs. Crystallography and molecular modeling have recently been applied to the design of V3-scaffold immunogens that contain variants of the generic V3 structure and several such immunogens have been synthesized and tested for antigenicity, Additionally, immunogenicity studies in rabbits show their ability to induce cross-clade neutralizing antibodies. Similar methods are being applied to the design of QNE-scaffold immunogens. The data indicate induction of neutralizing antibodies to conserved epitopes in variable regions, providing a paradigm for further development of rationally-designed HIV vaccines.

Copyright © 2011 Wolters Kluwer Health, Inc. All rights reserved.