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Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis (TB) is responsible for millions of deaths annually. BCG, the only vaccine against TB, fails to evoke memory response and is ineffective to provide protection among adults. The emergence of multi drug resistant strains of M.tb has necessitated development of new vaccines that can confer wider degree and long-term protection against TB. In this study, we have designed a novel multi-epitope vaccine (MEV) using the M.tb proteins, Rv1507A, Rv1509, Rv1954A and Rv2231A that are not only unique to this pathogen but are hallmark as these modulate different aspects of M.tb physiology. Rv1507A and Rv1954A elicit memory response in host while Rv1509 and Rv2231A have roles in virulence. These four proteins were chosen so as to develop a MEV that fills the gaps in existing vaccine against TB. We carried out in-silico analyses of various combinations of epitopes from these proteins, after codon optimization, to ensure that there is no toxicity and allergenicity while maintaining the highest level of immunogenicity of the MEV construct. Two MEV constructs were designed which can pair with different TLR-binding adjuvants: Laterosporulin (TLR-4) and PorB (TLR-2). In silico analysis of the MEV constructs revealed favorable biophysical and physicochemical properties, stability in structure and strong interactions with TLR receptors, suggesting their potential to trigger a robust immune response. Immunological simulations showed that MEV elicits robust immune response and exhibits nearly 90% coverage for global population due to its conserved nature. This study provides an important lead that can be validated through in vitro and in vivo assays, which may translate into tangible vaccine against TB.