Identification of T-cell epitopes for vaccine targets against melioidosis in North East Thailand. (360G-Wellcome-100174_Z_12_C)

A greater understanding of immunity to infectious diseases is desirable to improve treatments and vaccine design, especially for intra-cellular organisms which are harder to prevent and cure. One such organism is Burkholderia pseudomallei, a Gram negative bacterium which causes melioidosis in humans which carries a high mortality. The goal of this study is to demonstrate the CD8 response in patients acutely unwell with melioidosis and define key epitopes for vaccine design. 280 patients with ac ute melioidosis in North East Thailand will be studied, both with and without diabetes mellitus. Peripheral blood mononuclear cells will be isolated locally and used to evaluate T-cell responses by ex vivo IFN-gamma ELISPOT and flow cytometry to a panel of candidate proteins and peptides from B.pseudomallei. Cells from people with diabetes in the region and from unexposed healthy control subjects will be used as controls. Information from HLA typing and from the current consortium at the Immune Epitope Database will be used to identify candidate proteins and peptides, and responses to 9-mer peptides will be studied. Other studies of neutrophil function and acute phase response will be studied in parallel to produce a unified dataset covering several aspects of innate and adaptive immune responses.