Immunotherapy of MDR-TB with IgA and molecular engineering of antibodies with enhanced functions

Speaker Professor Rajko Reljic, Institute for Infection and Immunity, St George’s University of London

Title Immunotherapy of MDR-TB with IgA and molecular engineering of antibodies with enhanced functions

Host Hannah Gould and Jim McDonnell

 

Abstract Antibodies play a key role in protective immunity. Yet, some intracellular pathogens, such as Mycobacterium tuberculosis, somewhat contentiously appear to remain beyond their reach. However, these intracellular pathogens do become released from infected necrotic cells, and this provides a window of opportunity for antibodies to intercept them. TB, and especially multidrug-resistant TB (MDR-TB) is notoriously difficult to treat, and additional treatments are urgently required to improve the unsatisfactory cure rates and prevent clinical relapses. We have developed a form of combined immunotherapy based on IgA antibodies and interferon gamma, which in the mouse model of aerosol infection substantially reduced the lung bacterial burden of MDR-TB. The mechanism involved enhanced opsonophagocytic uptake of free bacteria and subsequently increased bactericidal activity by the host cells. Furthermore, we are also developing recombinant forms of ‘gain-of-function’ polymeric antibodies with enhanced biological activities. By virtue of their specific targeting of the Fc-receptors on antigen-presenting cells, these polymeric IgG-Fc fusion proteins have shown a significant promise as novel vaccine delivery systems against several infections, including TB, dengue and SARS-CoV2. Such antibody-based vaccine platforms offer the advantage of being self-adjuvanting and thus not requiring exogenous adjuvants to induce protective immunity.