Synthesis of Multicomponent Peptide-Based Vaccine Candidates against Group A Streptococcus
Waleed M. Hussein A D , Jiaxin Xu A , Pavla Simerska A and Istvan Toth A B C DA School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Qld 4072, Australia.
B Institute for Molecular Bioscience, The University of Queensland, Brisbane, Qld 4072, Australia.
C School of Pharmacy, The University of Queensland, Brisbane, Qld 4072, Australia.
D Corresponding authors. Email: w.hussein@uq.edu.au; i.toth@uq.edu.au
Australian Journal of Chemistry 70(2) 184-190 https://doi.org/10.1071/CH16501
Submitted: 8 September 2016 Accepted: 17 October 2016 Published: 7 November 2016
Abstract
Group A streptococcus (GAS; Streptococcus pyogenes), known as the ‘flesh-eating bacterium’, is a human bacterial pathogen that normally causes benign infections (e.g. sore throat and pyoderma), but is also responsible for severe invasive infections (e.g. ‘flesh-eating’ disease and toxic shock syndrome), heart disease, and kidney failure. A safe commercial GAS vaccine is yet to be developed. Individual GAS antigens demonstrate potential universal expression across all GAS serotypes (>200 known), with dramatically reduced concern for autoimmune complications, and compelling efficacy in preclinical testing in mice. In this study, we developed a stepwise conjugation strategy, copper-catalysed alkyne–azide cycloaddition reaction (CuAAC), followed by mercapto–maleimide conjugation, to synthesise a multiantigenic, self-adjuvanting, peptide-based vaccine candidate against GAS. This multiantigenic vaccine includes two GAS antigens, J8 and NS1, a T-helper epitope, PADRE, and a self-adjuvanting moiety, dipalmitoyl serine.
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