Research Projects

The management of latent tuberculosis infection is crucial for TB control, as dormant bacilli are a significant reservoir of potential cases. M.tuberculosis dormancy regulon (DosR regulon) proteins are highly expressed in latent infection and have been found to produce strong Th1 memory responses in PBMC of active tuberculosis patients and their healthy contacts. These proteins activate macrophages through TLR2 signaling and stimulate higher numbers of IFN-gamma+ CD4 and IFN-gamma+CD8 lymphocytes in PBMC of active tuberculosis patients and their healthy contacts. The researchers hypothesized that a fusion multiepitope construct of these proteins with identified promiscuous antigenic epitopes could both act as adjuvant and/or a vaccine candidate. In silico evaluation predicted good TLR2 and TLR 4 interactions, and further studies showed them to interact with both common MHC Class I and II molecules and produce proinflammatory cytokines and Th1 immunogenic response. The objective was to see the immunogenic potential and protective efficacy of these constructs in mouse models of tuberculosis and low dose Mtb aerosol challenge studies. The vaccine constructs containing both the protein and the immunogenic epitopes constitute an adjuvant/vaccine combination and if found immunogenic and protective, can be taken up for development of improved vaccines against active or latent TB or could act as an adjuvant in different vaccine formulations.