Download or read book Conformationally Restricted Synthetic AIDS Vaccine written by and published by . This book was released on 2001 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: It was proposed to develop a structure-based approach for synthetic vaccine development designed to recapitulate the activities of potent neutralizing monoclonal antibodies (MAbs) using constrained peptides as immunogens. We focused on two antibodies, a MAb 58.2 that binds a sequential V3 epitope and IgG bl2 that binds a discontinuous epitope, both on HIV-1 gp120. We validated the structure-based approach with a V3 mimetic using MAb 58.2 and demonstrated the enormous effect that peptide conformation can have on affinity and immunogenicity. We were unable to mimic the more challenging discontinuous IgG bl2 epitope despite considerable effort. The enormous affinity enhancements we observed for the constrained V3 peptide and dearth of potent HIV-1 neutralizing antibodies, particularly those specific for sequential epitopes, led us to an important discovery. It suggested that new antibodies might be identified with constrained peptides that go undetected with peptides. It was found that several helix-stabilized gpl20 peptides detect new antibodies that go undetected with linear peptides implying a general phenomenon. Constrained peptides, tailored to mimic short, sequential regions of proposed neutralization sites might be used to widen the selection of template antibodies best suited for synthetic vaccine development.