Despite being curable, Tuberculosis (TB) affects 10 million people annually and remains in the top 10 causes of fatality worldwide in recent years [1]. 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]. To cover all of the pathogen subtypes, the chosen epitope must be highly conserved. 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 region of difference 1, an essential determinant of mycobacterial virulence and is present in pathogenic Mycobacterium tuberculosis (Mtb) but absent in BCG [3]. The first twenty amino acids of ESAT-6, (ESAT-6(1-20), MTEQQWNFAGIEAAASAIQG) are widely recognized by CD4+ T cell, a vital host defense in combatting Mtb infection [4]. However, ESAT-6 has inherently low immunogenicity and require a suitable adjuvant or delivery system to evoke sufficient immune response. Polyacrylate and polyhydrophobic amino acid based delivery system have proven their efficacy to trigger eradication of tumours in mice [5, 6, 7]. As the currently available adjuvants are toxic with adverse reaction potentials, we aimed to conjugate ESAT-6(1-20) with a novel dendritic polyacrylate polymer or polyhydrophobic amino acid delivery system having self-adjuvanting and self-assembling properties for the development of a novel peptide-based subunit vaccine against TB.
Acknowledgements
This work was supported by the National Health and Medical Research Council, Australia (NHMRC Program Grant: 1132975).