Abstract
Melioidosis is a tropical infectious disease caused by Burkholderia pseudomallei that results in high mortality. Hemolysin co-regulated protein 1 (Hcp1) and O-polysaccharide (OPS) are vaccine candidates and potential diagnostic antigens. The correlation of classes/subclasses of antibodies against these antigens with clinical characteristics of melioidosis patients is unknown. Antibodies in plasma samples from melioidosis patients and healthy donors were quantified by ELISA and compared with clinical features. In melioidosis patients, Hcp1 induced high IgG levels. OPS induced high IgG and IgA levels. The area under receiver operating characteristic curve (AUROCC) to discriminate melioidosis cases from healthy donors was highest for anti-Hcp1 IgG (0.92) compared to anti-Hcp1 IgA or IgM. In contrast, AUROCC for anti-OPS for IgG (0.91) and IgA (0.92) were comparable. Anti-Hcp1 IgG1 and anti-OPS IgG2 had the greatest AUROCCs (0.87 and 0.95, respectively) compared to other IgG subclasses for each antigen. Survivors had significantly higher anti-Hcp1 IgG3 levels than non-survivors. Male melioidosis patients with diabetes had higher anti-OPS IgA levels than males without diabetes. Thus, diverse and specific antibody responses are associated with distinct clinical characteristics in melioidosis, confirming the diagnostic utility of these responses and providing new insights into immune mechanisms.
Highlights
Melioidosis is an infectious disease caused by Burkholderia pseudomallei, an environmental Gram-negative bacterium and CDC Tier 1 select agent
We observed that the median optical density (OD) values of IgA, IgM and IgG responses to Hcp[1] and OPS for melioidosis patients were significantly higher than for Thai healthy donors (P < 0.05 for all comparisons between melioidosis group versus Thai healthy donors group)
Hcp[1] and OPS expressed by B. pseudomallei are potential diagnostic antigens and vaccine candidates for melioidosis[16,17,18]
Summary
Melioidosis is an infectious disease caused by Burkholderia pseudomallei, an environmental Gram-negative bacterium and CDC Tier 1 select agent. Other studies in Malaysia used culture filtrate antigen (CFA) for serology studies of septicemic melioidosis patients and suggest a role for different classes and subclasses of antibody responses in septicemic and localized melioidosis[10,11]. We demonstrated that rapid ELISAs based on detection of IgG to recombinant hemolysin co-regulated protein 1 (Hcp1) and O-polysaccharide (OPS) antigens of B. pseudomallei have diagnostic potential in melioidosis[13,14]. B. pseudomallei may induce different classes and subclasses of antibody responses to Hcp[1] and OPS antigens. We hypothesized that IgA, IgM and IgG responses and IgG subclasses are induced differentially by Hcp[1] and OPS antigens and may be correlated with characteristics of melioidosis patients
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