A structure-based strategy for epitope discovery in burkholderia pseudomallei OppA antigen

Patricia Lassaux, Claudio Peri, Mario Ferrer-Navarro, Louise J. Gourlay, Alessandro Gori, Oscar Conchillo-Solé, Darawan Rinchai, Ganjana Lertmemongkolchai, Renato Longhi, Xavier Daura, Giorgio Colombo, Martino Bolognesi

Research output: Contribution to journalArticleResearchpeer-review

35 Citations (Scopus)

Abstract

We present an approach integrating structural and computational biology with immunological tests to identify epitopes in the OppA antigen from the Gram-negative pathogen Burkholderia pseudomallei, the etiological agent of melioidosis. The crystal structure of OppABp, reported here at 2.1 Å resolution, was the basis for a computational analysis that identified three potential epitopes. In parallel, antigen proteolysis and immunocapturing allowed us to identify three additional peptides. All six potential epitopes were synthesized as free peptides and tested for their immunoreactivity against sera from healthy seronegative, healthy seropositive, and recovered melioidosis patients. Three synthetic peptides allowed the different patient groups to be distinguished, underlining the potential of this approach. Extension of the computational analysis, including energy-based decomposition methods, allowed rationalizing results of the predictive analyses and the immunocapture epitope mapping. Our results illustrate a structure-based epitope discovery process, whose application may expand our perspectives in the diagnostic and vaccine design fields. © 2013 Elsevier Ltd.
Original languageEnglish
Pages (from-to)167-175
JournalStructure
Volume21
DOIs
Publication statusPublished - 8 Jan 2013

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