Poster Presentation Asia-Pacific Vaccine and Immunotherapy Congress 2023

Towards development of novel peptide subunit vaccine for Tuberculosis   (#120)

Viet Tram Duong 1 , Mariusz Skwarczynski 1 , Istvan Toth 1
  1. University of Queensland, St Lucia, QLD, QUEENSLAND, Australia

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 haveproven theirefficacy 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)witha  novel dendritic polyacrylate polymeror polyhydrophobic amino acid delivery systemhaving self-adjuvantingand self-assemblingproperties for the development of a novelpeptide-based subunit vaccine against TB.

  1. 1. World Health Organization, Global tuberculosis report 2019.
  2. 2. Skwarczynski, M. and I. Toth, Peptide based synthetic vaccines. Chemical Science, 7(2): 842-854 (2016).
  3. 3. Samten, B., X. Wang, and P.F. Barnes, Immune regulatory activities of early secreted antigenic target of 6-kD protein of Mycobacterium tuberculosis and implications for tuberculosis vaccine design. Tuberculosis, S114-S118, 2011.
  4. 4. Lindestam Arlehamn, C.S., et al., Antigens for CD4 and CD8 T cells in tuberculosis. Cold Spring Harbor perspectives in medicine. 4(7): a018465-a018465 (2014)
  5. 5. Liu TY, Hussein WM, Jia Z, Ziora ZM, McMillan NA, Monteiro MJ, Toth I, Skwarczynski M. Self-adjuvanting polymer peptide conjugates as therapeutic vaccine candidates against cervical cancer. Biomacromolecules. 14(8), 2798-2806 (2013).
  6. 6. Liu TY, Hussein WM, Jia Z, Ziora ZM, McMillan NA, Monteiro MJ, Toth I, Skwarczynski M. et al. Polyacrylate-based delivery delivery system for self-adjuvanting anticancer peptide vaccine. Journal of Medicinal Chemistry. 58(2), 888-896 (2015).
  7. 7. Liu TY, Giddam AK, Hussein WM, Jia Z, McMillan NA, Monteiro MJ, Toth I, Skwarczynski M. Self-adjuvanting therapeutic peptide based vaccine induce CD8+ cytotoxic T lymphocyte responses in a murine human papillomavirus tumor model. Current Drug Delivery. 12(1), 3-8 (2015).