A small molecule based immunotherapy targeting IL-10/STAT3 praxis to augment the potential of rBCG30 vaccine against experimental tuberculosis

Several recent studies have contributed to our understanding of the need for host directed immunotherapeutic strategies against Mycobacterium tuberculosis (Mtb), either concomitantly with classical chemotherapy or as standalone intervention. Nevertheless, most of these studies were focused on enhancing chemotherapeutic potential of standard anti-tuberculosis chemotherapy and only few were aimed towards improving prophylactic immunity offered either by BCG or its potential replacements. In the present study we tried to address the potential gap with the aim to improve anti-TB immunity offered by 2nd generation rBCG30 vaccine. We attempted to bolster rBCG30 invoked anti-TB immunity in mice through modulation of the IL-10/STAT3 interaction mediated anti inflammatory program. An immunomodulator of IL-10/STAT3 signaling axis was administered in immunized mice to reinforce the anti-pathogen capabilities of mononuclear phagocyte system with expectation to improve T cell mediated secondary immune responses. We envisage that modulation of this crucial praxis may result in reduced expansion of pathogen permissive AAMs/AADCs (Alternatively Activated Monocytes/Macrophages/DCs) and augmented abundance of pro-inflammatory CAMs/CADCs (Classically Activated Monocytes/Macrophages/DCs), the cells that resist establishment of successful Mtb infection. The study was also aimed towards generating optimum activated APCs early either after vaccination or infection, which can process and present mycobacterial antigens more efficiently to T cells.