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14th International AIDS ConferenceBarcelona, Spain — July 7-12, 2002 |
Int Conf AIDS. 2002 Jul 7-12;14:Abstract No. MoOrA1089
BACKGROUND: Monoclonal antibodies (mAbs) have been identified that bind to highly conserved regions on HIV-1 gp120 and are able to neutralize a broad range of different HIV-1 isolates. The binding site for one of these mAbs, termed 17b, overlaps with the coreceptor binding site and single amino acids relevant for binding have been identified by site-directed mutagenesis and in the crystal structure of the gp120-17b complex. In this study mAb 17b was used to identify small peptide ligands that are able to mimic the conformational epitope involved in coreceptor binding of gp120.
Materials and
METHODS: Phage displayed random peptide libraries have been screened with mAb 17b to identify phagotopes mimicking the mAb epitope and therefore the coreceptor binding site. Identified clones were evaluated by ELISA and corresponding motifs in gp120 were changed to alanines.
RESULTS: Several phage clones have been identified that specifically bind to mAb 17b. These clones were sequenced and aligned to the tertiary structure of gp120. The sequences of the mimotopes contain motifs from gp120 that were shown to relevant for 17b and coreceptor binding in earlier studies. Mutants of JR-CSF have been generated that have the identified motifs in gp120 replaced by alanines to evaluate the role of the motifs in mAb and coreceptor binding. Additionally, immunization studies are under way to generate antiserum to the identified mimotopes. These antisera will be used in HIV-1 neutralization studies to test for a broadly neutralizing capacity.
CONCLUSIONS: Short peptide sequences have been identified that specifically bind to mAb 17b. The peptide sequences can be aligned to gp120 and are consistent with earlier data on 17b. These peptides are mimotopes of the 17b eptitope, which is relevant in viral entry and highly conserved among various HIV-1 isolates. Therefore the mimotopes are excellent candidates as immunogens and interesting targets to interfere with the HIV-1 entry process.
Presenting author: Christoph Koenigs
1Georg-Speyer-Haus, Georg-Speyer-Haus, Paul-Ehrlich-Str. 42-44, 60596 Frankfurt am Main, Germany.
2MPI for Biophysical Chemistry, Göttingen, Germany.
3Tulane University Medical Centre, New Orleans, Germany.
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MoOrA1089
Copyright © 2002 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.
