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.
Exploiting the Burkholderia pseudomallei acute phase antigen BPSL2765 for structure-based epitope discovery/design in structural vaccinology / L.J. Gourlay, C. Peri, M. Ferrer-Navarro, O. Conchillo-Solé, A. Gori, D. Rinchai, R.J. Thomas, O.L. Champion, S.L. Michell, C. Kewcharoenwong, A. Nithichanon, P. Lassaux, L. Perletti, R. Longhi, G. Lertmemongkolchai, R.W. Titball, X. Daura, G. Colombo, M. Bolognesi, C. Peri. - In: CHEMISTRY & BIOLOGY. - ISSN 1074-5521. - 20:9(2013 Sep 19), pp. 1147-1156.
|Titolo:||Exploiting the Burkholderia pseudomallei acute phase antigen BPSL2765 for structure-based epitope discovery/design in structural vaccinology|
|Parole Chiave:||Protein antigen; Antigen 3D structure; structural vaccinology; computational biology; epitope discovery.|
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
|Data di pubblicazione:||19-set-2013|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.chembiol.2013.07.010|
|Appare nelle tipologie:||01 - Articolo su periodico|