Dr Panjaporn Chaichana
Mahidol-Oxford Tropical Medicine Research Unit, Thailand
Identification of protective antibody profiles for vaccine development against melioidosis
Melioidosis is a major cause of fatal community-acquired sepsis in tropical regions, caused by the Gram-negative bacterium Burkholderia pseudomallei (Bp). The mortality rate of inpatients exceeds 35% in endemic areas. Bp is intrinsically resistant to first-line antibiotics rendering the disease difficult to cure, and relapses occur despite prolonged treatment with intravenous antibiotics. Antibody-based vaccine is a promising strategy for controlling the acute Bp infection and reducing mortality.
This project aims to develop and optimize approaches to systematically measure protective profiles of antibodies to the Bp infection for vaccine design and development. We used available serum samples from 136 patients with culture-confirmed acute melioidosis in a longitudinal study in Ubon Ratchathani to explore measurable biophysical and functional characteristics of Bp-specific protective antibodies.
Our result demonstrates that protection against death in acute melioidosis patients is associated with high levels of Bp-specific IgG2 subclass, enhanced phagocytosis and intracellular growth inhibition in macrophages. In addition, we constructed human monoclonal antibodies from plasmablast dereived from the patients who survived melioidosis to investigate antigenic lanscape in natural infection. We will test these monoclonal antibodies using our functional assays. The finding from this study will evaluate the potential role of antibodies as a novel vaccine and therapy for acute melioidosis.
I am a postdoctoral fellow at MORU under the supervision of Prof Susanna Dunachie. My research interest is to understand antibody responses to melioidosis. Last year, I was awarded the first round of VALIDATE pump-priming grant to establish assays to explore antibody features and functional activities in Burkholderia pseudomallei infection including antibody-dependent cellular phagocytosis (ADCP), antibody-dependent cellular cytotoxicity (ADCC) and growth inhibition assays. These measurements would help identify antibody profiles that are associated with protection against fatal melioidosis or help evaluate induced antibody responses after vaccination. My current work is to construct monoclonal antibodies from plasmablast of patients with acute melioidosis for delineating the antigenic landscape during natural B. pseudomallei infection. Outcomes from 2 projects would provide important insight on protective responses for development of antibody-based vaccine against melioidosis.