Discovering anti-Mycobacterium tuberculosis monoclonal antibodies from TB-exposed, disease-free individual
Led by Dr Shi-Hsia HWA (National Institute of Allergy and Infectious Diseases (NIAID), United States of America), with Prof Robert J Wilkinson (University of Cape Town (UCT), South Africa)
Project Aim
Monoclonal antibodies have been used to prevent and treat a number of infectious diseases such as COVID-19. We know that people who are exposed to Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis (TB), develop antibody responses that specifically target these bacteria. However, we do not know which surface molecules of Mtb are important antigens (targets) for protective antibody responses for preventing or controlling infection. Some people seem to be naturally resistant to TB, as they do not develop TB even after living with household members who are TB patients. A previous study monitored some of these household contacts for several years and collected blood samples from them. We plan to select the individual donors who have the strongest Mtb-binding antibodies in their plasma, and isolate the B cells that produce those antibodies. We will use whole inactivated (killed) bacteria to select these B cells, which could enable us to find previously unknown antigens on the bacterial surface, instead of being biased toward only known antigens. We can then sequence the antibody genes from these cells and produce concentrated, purified monoclonal antibodies and test them to determine which ones can inhibit live Mtb bacteria.
These antibodies could be administered to TB patients in addition to the current antibiotic regimens to improve and speed up treatment, which takes months even for drug-sensitive infections, and could also be helpful for people infected with drug-resistant strains of Mtb. The antibodies could also be administered prophylactically to individuals at high risk of exposure, such as household members of TB patients, healthcare workers, and travellers to high-prevalence countries. In addition, identifying which antigens on the bacteria are targeted by protective antibodies will provide valuable information to other researchers developing the next generation of TB vaccines, as these antigens could then be included in experimental vaccines.
