Poster Presentation 8th Modern Solid Phase Peptide Synthesis & Its Applications Symposium 2022

Development of peptide based subunit vaccine for prevention of Tuberculosis (#109)

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 pulmonary TB, the most prevalent form of 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]. The early secretory antigenic target 6 kDa (ESAT-6) is an essential determinant of mycobacterium tuberculosis (Mtb) virulence [3]. The first twenty amino acids of ESAT-6, (ESAT-6(1-20)) 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 based delivery system has proven its efficacy to trigger eradication of tumours in mice [5, 6, 7]. As the currently available adjuvants are toxic with adverse reaction potentials, we conjugated ESAT-6(1-20) with a  novel dendritic polyacrylate polymer having self-adjuvanting and self-assembling properties for the development of a peptide-based subunit vaccine against TB without the use of any adjuvants. Peptides were synthesized using manual stepwise solid phase peptide synthesis via Fmoc chemistry. Peptide-polymer conjugation was carried out using copper wired catalyzed alkyne-azide cycloaddition reaction. The average particle size is found to be around 650 nm with an average polydispersity index of 0.22. Following DLS analysis, self-assembled microparticles in water were lyophilized for elemental analysis. The degree of substitution was approximately 4.5 and the conjugation efficacy was 56%. Therefor we have successfully synthesized a nanoparticle based subunit vaccine for TB.

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