Establishment of a functional assay panel to evaluate the role of antibodies in defence against melioidosis and tuberculosis
Led by Dr Panjaporn Chaichana (MORU), with Prof Susanna Dunachie (University of Oxford), and Assoc Prof Helen Fletcher (LSHTM)
Melioidosis is an infectious disease and a major cause of death in lower and middle income countries including Thailand. It is caused by a bacterium named Burkholderia pseudomallei mostly found in rice paddies. Each year thousands of people living in environments contaminated with the bacteria are infected, and nearly half of them die. The bacterium is classified as a potential bioweapon, and commonly-used antibiotics cannot completely cure the disease.
The symptoms of the disease are more severe and deadly in patients whose immune systems work abnormally, including people with diabetes, renal disease, alcoholism and increased age. Antibody-based strategies are the most promising ways to prevent and treat melioidosis. We wish to identify which types of antibody provide protection against disease and how they work.
B. pseudomallei has some common features with the bacterial cause of tuberculosis: Mycobacterium tuberculosis, including the intracellular nature of the bacteria and an overlap in clinical disease such as lung symptoms and abscesses formation. This project will make the most of these similarities by combining experimental expertise in the development of antibody assays to define protective antibody profiles.
First, we plan to develop five tests that measure important actions of antibodies in protection against bacterial infection, which have never been done in the melioidosis field. This will be a collaboration between a Thai scientist and scientists at the London School of Hygiene and Tropical Medicine, who have developed expertise in tuberculosis immunology. Then we will measure and compare the actions of antibodies between patients who survived melioidosis and those who did not survive, to identify significant factors in protective responses. The work on melioidosis will in turn inform the further development of antibody assays for the TB. Results from this study will help develop vaccines and new antibody-based therapies for both diseases.
We have successfully created assays that can measure key antibody activities involved in protection against death in melioidosis patients. Results from these assays indicate that melioidosis patients have a tendency to survive the disease if they have high levels of IgG antibody subclass 2 (IgG2). Patients were more likely to survive if their antibodies demonstrate the potential to bring live B. pseudomallei into macrophage cells. The findings in this project emphasize the important of antibody functions in melioidosis, and provide vital functional assays for vaccine development to link laboratory models to the target patient population.