Rapid Fire 14th Australian Peptide Conference 2022

Poly(hydrophobic amino acids) as a Self-Adjuvanting Delivery System for Peptide Vaccines (#20)

Mariusz Skwarczynski 1 , Istvan Toth 1 2 3
  1. School of Chemistry and Molecular Biosciences, The University of Queensland , St Lucia, QLD 4072, Australia
  2. School of Pharmacy, University of Queensland, Brisbane, QLD, Australia
  3. Institute of Molecular Bioscience, The University of Queensland, St Lucia, Queensland 4072, Australia

Vaccines based on the whole pathogen as well as protein-based vaccines are able to deliver protection against variety of pathogens; however, they are often not fully safe and may induce undesirable immune responses (e.g. inflammation, allergy, etc). Moreover some vaccines must use even smaller component than protein to avoid triggering autoimmune responses, for example all modern vaccines against Group A Streptococcus (GAS) that have entered clinical are based on peptide antigens. Thus, peptide-based vaccine can solve above problems; however, they need powerfully adjuvants (immunostimulators), which are usually bacteria derived and are associated with some toxicity.

Previously we have demonstrated that hydrophobic dendritic poly(tert-butyl acrylate) can be conjugated to a variety of peptides epitopes, including GAS-derived peptides, self-assembled to form particles, which can induce potent humoral and cellular immune responses. However, these polymers were not biodegradable, had undefined stereochemistry and number of unit repeats. This typical variability of polymer structure may affect in vitro and in vivo efficacy of vaccine and therefore might not be suitable for clinical trials.

Here we demonstrated that conjugation of peptide antigen to polymerized hydrophoic amino acids can form nanoparticles, which can induce strong humoral immune responses [1,2]. This new polymeric system is fully-defined, has no chain or stereochemistry variability, and biodegradable to non-toxic natural amino acids. It can be customized to adopt the polymer to selected antigen, for example to produce nanoparticle of desired size. Therefore, the system is expected to find application in the vast variety of vaccines against infectious diseases.

 

 

  1. Skwarczynski, M.; Zhao, G.; Boer, J. C.; Ozberk, V.; Azuar, A.; Cruz, J. G.; Giddam, A. K.; Khalil, Z. G.; Pandey, M.; Shibu, M. A.; Hussein, W. M.; Nevagi, R. J.; Batzloff, M. R.; Wells, J. W.; Capon, R. J.; Plebanski, M.; Good, M. F.; Toth I. Poly(amino acids) as a Potent Self-adjuvanting Delivery System for Peptide-based Nanovaccines Science Advances 2020, 6, eaax2285.
  2. Azuar, A.; Li, Z.; Shibu, M. A.; Zhao, L.; Luo, Y.; Shalash, A. O.; Khalil, Z. G.; Capon, R. J.; Hussein, W. M.; Toth I.; Skwarczynski, M. Poly(hydrophobic amino acid)-based self-adjuvanting nanoparticles for Group A Streptococcus vaccine delivery. J. Med. Chem., 2021, 64, 2648-2658.