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Abstract

In tuberculosis-endemic population, the main reason for the failure of BCG vaccine is the obstacle caused by non-tuberculous
mycobacteria and helminths in its processing and presentation. Usually, peptides do not require extensive antigen processing
since they can bind to major histocompatibility complex molecules and therefore can be directly presented to T cells. As
a result, peptide vaccines can surmount the problems associated with BCG failure. It is well-established fact that not only
adaptive but also innate immunity plays a crucial role in protection against tuberculosis. Hence we have constructed a novel
lipopeptide vaccine by linking promiscuous CD4 and CD8 epitopes of Mycobacterium tuberculosis to Pam2Cys, a Toll like
Receptor-2 agonist. This lipopeptide has unique property of self-adjuvanting and concurrently activating both innate and
adaptive immunity. The vaccine binds directly to MHC I and MHC II molecules and TLR-2. It stimulates dendritic cells to
secrete cytokines, upregulates the expression of costimulatory molecules and significantly augments their ability to present
antigen to T cells. Further, the vaccinated animals impart robust and enduring memory Th1 and Th17 response. The protection
observed is significantly better than BCG. This lipidated-peptide vaccine is unique since it overcomes MHC barriers and
evokes immune response irrespective of HLA polymorphism in human. This vaccine has enough potential to induce longlasting
protection against Mycobacterium tuberculosis. Therefore it can be a potent future vaccine candidate for controlling
tuberculosis.

Biography