By combining large-scale antibody microarrays and assays of T cell-mediated immunity, we identified a panel of novel B. pseudomallei proteins that show distinct patterns of reactivity in different stages of human melioidosis. These proteins may be useful candidates for development of subunit-based vaccines and in monitoring the risks of treatment failure and relapse.
BackgroundInfection with the Gram-negative bacterium Burkholderia pseudomallei is an important cause of community-acquired lethal sepsis in endemic regions in southeast Asia and northern Australia and is increasingly reported in other tropical areas. In animal models, production of interferon-gamma (IFN-γ) is critical for resistance, but in humans the characteristics of IFN-γ production and the bacterial antigens that are recognized by the cell-mediated immune response have not been defined.MethodsPeripheral blood from 133 healthy individuals who lived in the endemic area and had no history of melioidosis, 60 patients who had recovered from melioidosis, and 31 other patient control subjects were stimulated by whole bacteria or purified bacterial proteins in vitro, and IFN-γ responses were analyzed by ELISPOT and flow cytometry.Findings B. pseudomallei was a potent activator of human peripheral blood NK cells for innate production of IFN-γ. In addition, healthy individuals with serological evidence of exposure to B. pseudomallei and patients recovered from active melioidosis developed CD4+ (and CD8+) T cells that recognized whole bacteria and purified proteins LolC, OppA, and PotF, members of the B. pseudomallei ABC transporter family. This response was primarily mediated by terminally differentiated T cells of the effector–memory (TEMRA) phenotype and correlated with the titer of anti-B. pseudomallei antibodies in the serum.ConclusionsIndividuals living in a melioidosis-endemic region show clear evidence of T cell priming for the ability to make IFN-γ that correlates with their serological status. The ability to detect T cell responses to defined B. pseudomallei proteins in large numbers of individuals now provides the opportunity to screen candidate antigens for inclusion in protein or polysaccharide–conjugate subunit vaccines against this important but neglected disease.
This study aimed to determine the antibody and T cell responses to Burkholderia pseudomallei (B. pseudomallei) of healthy individuals in endemic areas, and recovered melioidosis patients in order to select candidate vaccine antigens. A protein microarray of 154 (B. pseudomallei) proteins was probed with plasma from healthy individuals (n=108) and recovered patients (n=72). The results showed that 27 proteins distinctively reacted with plasma from both groups suggesting that different responses occur following environmental exposure or clinical melioidosis. We also compared the responses according to their history of subsequent relapse and the average antibody response to BPSL2765 (putative OmpA family protein) was over 10 times higher in plasma from individuals who had only one episode of disease than those with recurrent melioidosis. A comparison of antibody and T-cell responses to five (B. pseudomallei) proteins revealed that BimA and flagellin induced responses which were similar between both groups but BPSS0530; a conserved hypothetical protein could induce T cell responses of healthy controls more than recovered melioidosis. By combining large scale antibody microarrays and assays of T cell mediated immunity, we have identified a panel of novel (B. pseudomallei) proteins which show distinct patterns of reactivity in different stages of human melioidosis. These proteins may be useful candidates for development of subunit based vaccines.
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