Exploiting the Burkholderia pseudomallei Acute Phase Antigen BPSL2765 for Structure-Based Epitope Discovery/Design in Structural Vaccinology

• Crystal structure of antigen PalBp as a structural vaccinology target
• Computational prediction and structure-based design of synthetic PalBp epitopes
• Synthetic epitope peptide is recognized by immune sera from melioidosis patients
• Epitope peptide elicits bactericidal antibodies, shown by agglutination/OPK tests

SummaryWe 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.

Graphical AbstractFigure optionsDownload high-quality image (166 K)Download as PowerPoint slide