Poster Presentation 7th Modern Solid Phase Peptide Synthesis & Its Applications Symposium 2019

Development of polymer-based nanoparticulate intranasal lipopeptide vaccine constructs against group A streptococcus (#123)

Reshma Jayprakash Nevagi 1 , Wei Dai 2 , Zeinab G Khalil 3 4 , Waleed M Hussein 2 , Robert J Capon 3 , Mariusz Skwarczynski 2 , Istvan Toth 2 3 5
  1. School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia, QLD, Australia
  2. School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD, Australia
  3. Institute for Molecular Bioscience, The University of Queensland, St Lucia, QLD, Australia
  4. Diamantina Institute, The University of Queensland, Woolloongabba, QLD, Australia
  5. School of Pharmacy, The University of Queensland, Woolloongabba, QLD, Australia

Group A streptococcus (GAS) is a gram-positive bacterium that is responsible for broad range of human diseases such as pharyngitis, impetigo, pneumonia, bacteremia, toxic shock syndrome, acute rheumatic fever (ARF) and rheumatic heart disease. Vaccines, rather than antibiotics, are expected to be efficacious for the prevention of GAS related infections. So far, there is no commercial vaccine available against GAS. Traditional vaccines composed of live/attenuated or killed microorganism have been effective against diseases such as influenza, smallpox and chicken pox. However, whole organism-based vaccine is not feasible for GAS due to existence of more than 200 serotypes. Cell surface M-protein is the major virulent factor of GAS. But, M-protein based vaccine is predicted to induce autoimmune response due to structural similarity with human cardiac myosin. Thus, synthetic peptide vaccines based on epitopes derived from conserved region of M-protein are expected to be efficient to provide protection against GAS. However, peptide epitopes alone are poorly immunogenic due to lack of pathogen associated structural patterns. Hence, adjuvants are often included in peptide vaccine to trigger immune response against peptide antigen. Lipids and polymers are known to possess adjuvanting property. Therefore, we developed a GAS peptide vaccine based on lipid and polymers combination strategy. We synthesised lipopeptides that included lipid moiety, GAS B-cell peptide epitope J8 (QAEDKVKQSREAKKQVEKALKQLEDKVQ) and universal T-helper epitope PADRE (AKFVAAWTLKAAA), which were further formulated into polymeric nanoparticles. For that purpose, lipopeptides were conjugated to anionic polymer via copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) “click” reaction. These anionic lipopeptide conjugates formed nanoparticles (200 nm, + 40 mV) via ionic-complexation with a cationic polymer, trimethyl chitosan. The lipopeptides formulated into nanoparticles were able to induce high systemic and mucosal IgG antibody titers upon intranasal immunisation in mice. The produced serum antibodies were opsonic against five strains of GAS.

  1. Nevagi, R. J.; Skwarczynski, M.; Toth, I. Polymers for Subunit Vaccine Delivery, European Polymer Journal, 114, 2019, 397-410.
  2. Nevagi, R. J.; Toth, I.; Skwarczynski, M. Peptide-based vaccines, In: Peptide Applications in Biomedicine, Biotechnology and Bioengineering, Woodhead publishing 2018, pp. 327-358.
  3. Nevagi, R. J.; Khalil, Z. G.; Hussein, W. M.; Powell, J.; Batzloff, M.; Capon, R. J.; Good, M.; Skwarczynski, M.; Toth, I. Polyglutamic acid-trimethyl chitosan-based intranasal peptide nano-vaccine induces potent immune responses against group A streptococcus, Acta Biomaterialia, 80, 2018, 278-287.
  4. Nevagi, R. J.; Dai, W., Khalil, Z. G.; Hussein, W. M.; Capon, R. J.; Skwarczynski, M.; Toth, I. Structure-activity relationship of group A streptococcus lipopeptide vaccine candidates in trimethyl chitosan-based self-adjuvanting delivery system, European journal of Medicinal Chemistry (submitted)
  5. M. Skwarczynski, I. Toth, Peptide-based synthetic vaccines, Chemical Science, 7 (2016) 842-854.