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

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

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Abstract

Summary 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.

Original languageEnglish
Pages (from-to)1147-1156
Number of pages10
JournalChemistry and Biology
Volume20
Issue number9
DOIs
Publication statusPublished - 19 Sep 2013

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Cite this

Gourlay, L. J., Peri, C., Ferrer-Navarro, M., Conchillo-Solé, O., Gori, A., Rinchai, D., Thomas, R. J., Champion, O. L., Michell, S. L., Kewcharoenwong, C., Nithichanon, A., Lassaux, P., Perletti, L., Longhi, R., Lertmemongkolchai, G., Titball, R. W., Daura, X., Colombo, G., & Bolognesi, M. (2013). Exploiting the burkholderia pseudomallei acute phase antigen BPSL2765 for structure-based epitope discovery/design in structural vaccinology. Chemistry and Biology, 20(9), 1147-1156. https://doi.org/10.1016/j.chembiol.2013.07.010