Exploiting the Burkholderia pseudomallei acute phase antigen BPSL2765 for structure-based epitope discovery/design in structural vaccinology.

Abstract

We solved the crystal structure of Burkholderia pseudomallei acute phase antigen BPSL2765 in the context of a structural vaccinology study, in the area of melioidosis vaccine development. Based on the structure, we applied a recently developed method for epitope design that combines computational epitope predictions with in vitro mapping experiments and successfully identified a consensus sequence within the antigen that, when engineered as a synthetic peptide, was selectively immunorecognized to the same extent as the recombinant protein in sera from melioidosis-affected subjects. Antibodies raised against the consensus peptide were successfully tested in opsonization bacterial killing experiments and antibody-dependent agglutination tests of B. pseudomallei. Our strategy represents a step in the development of immunodiagnostics, in the production of specific antibodies and in the optimization of antigens for vaccine development, starting from structural and physicochemical principles.

• Authors: Louise J Gourlay, Claudio Peri, Mario Ferrer-Navarro, Oscar Conchillo-Solé, Alessandro Gori, Darawan Rinchai, Rachael J Thomas, Olivia L Champion, Stephen L Michell, Chidchamai Kewcharoenwong, Arnone Nithichanon, Patricia Lassaux, Lucia Perletti, Renato Longhi, Ganjana Lertmemongkolchai, Richard W Titball, Xavier Daura, Giorgio Colombo, Martino Bolognesi
• Journal: Chemistry & biology (Chem Biol) Vol. 20 Issue 9 Pg. 1147-56 (Sep 19 2013) ISSN: 1879-1301 [Electronic] United States
• PMID: 23993463 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Antibodies
• Antigens, Bacterial
• Bacterial Proteins
• Bacterial Vaccines
• Epitopes
• Recombinant Proteins

Topics

• Antibodies (blood, immunology)
• Antigens, Bacterial (chemistry, immunology, metabolism)
• Bacterial Proteins (chemistry, genetics, immunology)
• Bacterial Vaccines (immunology)
• Burkholderia pseudomallei (immunology, metabolism)
• Crystallography, X-Ray
• Epitope Mapping
• Epitopes (chemistry, immunology, metabolism)
• Humans
• Molecular Dynamics Simulation
• Neutrophils (cytology, immunology)
• Phagocytosis
• Protein Structure, Tertiary
• Recombinant Proteins (biosynthesis, chemistry, immunology)