Tuberculosis(TB) affects 10 million people annually and is the leading cause of death from a single infectious agent [1]. Mycobacterium tuberculosis (Mtb), the infectious agent, typically infects the lung but can spread through the body and affect other organs as well. A person becomes infected after inhaling bacili droplets exhaled from active TB patients. The infected person can become ill immediately or carry the infection latently. Latent infection can be reactivated once the host immune system is weakened. Vaccination has been critical in saving lives and reduce the burden of many infectious diseases in the last century. The current Bacillus Calmette Guerin vaccine offers inconsistent protection against the most prevalent form of TB, pulmonary TB. Peptide based subunit vaccine is a promising approach to combat TB as it minimizes microbial components, still elicits the desired immune response and avoids pathogenic reversion which is possible in vaccines comprised of live attenuated pathogens [2]. T helper cells are crucial linker between innate and adaptive immunity and hence are vital in peptide based vaccine. Immune responses without the T-helper component are inconsistent in heterogenous population and memory responses are diminished. The early secretory antigenic target 6 kDa (ESAT-6) is encoded in the chromosomal locus of RD1, an essential determinant of mycobacterial virulence and is present in pathogenic Mtb but absent in BCG. However, ESAT-6 has inherently low immunogenicity and would require a suitable adjuvant or delivery system to evoke sufficient immune response. As the currently available adjuvants are toxic with adverse reaction potentials, we aimed to incorporate ESAT-6(1-20)into novel self-adjuvanting polyhydrophobic amino acid or polymer based delivery systems for the development of a peptide based nanovaccine against TB. We have successfully synthesized the peptide candidates via solid phase peptide synthesis and will continue to optimize the vaccine candidates formulation.