Abstract
Melioidosis is a neglected tropical disease with high mortality rate. It is caused by the Gram-negative, CDC category B select agent Burkholderia pseudomallei (B. ps) that is intrinsically resistant to first-line antibiotics. An antibody-based vaccine is likely to be the most effective control measure. Previous studies have demonstrated significant mechanistic roles of antibodies in protection against death in animal models, but data from human melioidosis is scarce. Herein, we used in-vitro antibody-dependent cellular phagocytosis and growth inhibition assays to assess the mechanism of protective antibodies in patients with acute melioidosis. We found that serum from patients who survived the disease enable more live B. ps to be engulfed by THP-1 derived macrophages (median 1.7 × 103 CFU/ml, IQR 1.1 × 103-2.5 × 103 CFU/ml) than serum from patients who did not survive (median 1.2 × 103 CFU/ml, IQR 0.7 × 103-1.8 × 103, p = 0.02). In addition, the intracellular growth rate of B. ps pre-opsonized with serum from survivors (median 7.89, IQR 5.58–10.85) was diminished when compared with those with serum from non-survivors (median 10.88, IQR 5.42–14.88, p = 0.04). However, the difference of intracellular bacterial growth rate failed to reach statistical significance when using purified IgG antibodies (p = 0.09). These results provide new insights into a mechanistic role of serum in protection against death in human melioidosis for antibody-based vaccine development.
Highlights
Melioidosis is well-recognized as a major cause of fatal community-acquired septicemia in northeast Thailand and north Australia (Chaowagul et al, 1989; Currie et al, 2000)
Antibody-Dependent Cellular Phagocytosis (ADCP) is important for the clearance of bacterial infection; we initially determined the opsonophagocytic activities of antibodies derived from patients in a monocyte cell line using flow cytometry
Serum samples were collected from acute melioidosis patients at a median of 5 days after admission, and antibodies against B. ps antigens in the serum were measured by ELISA
Summary
Melioidosis is well-recognized as a major cause of fatal community-acquired septicemia in northeast Thailand and north Australia (Chaowagul et al, 1989; Currie et al, 2000). The case fatality rate can exceed 40% in endemic regions. The causative agent of melioidosis is the facultative intracellular Gram-negative bacillus Burkholderia pseudomallei (B. ps), which is intrinsically resistant to commonly used antibiotics. Prolonged antibiotic regimens are required to control the infection. Effective vaccines against other polysaccharideencapsulated bacteria including Streptococcus pneumoniae, Neisseria meningitides, and Haemophilus influenzae type b rely on antibody-mediated protection (Snape et al, 2008; Pollard et al, 2009; Wahid et al, 2014), antibody-based vaccines are one of the most promising approaches to control B. ps infection
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
