Delivery of a peptide-based vaccine against Group A Streptococcus with the help of cell penetrating peptides — ASN Events

Delivery of a peptide-based vaccine against Group A Streptococcus with the help of cell penetrating peptides (#219)

Jieru Yang 1 , Armira Binti Azuar 1 , Istvan Toth 1 2 3 , Mariusz Skwarczynski 1
  1. School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD, Australia
  2. Institute of Molecular Biosciences, The University of Queensland, St Lucia, Queensland, Australia
  3. School of Pharmacy, The University of Queensland, Woolloongabba, QLD, Australia

Group A Streptococcus (GAS) is one of the most common human pathogens  responsible for a wide spectrum of diseases, ranging from noninvasive (pharyngitis, impetigo) to post-infectious autoimmune disorders (rheumatic fever and rheumatic heart disease)1. However, there are no licensed vaccines available for the prevention of GAS infection. Traditional vaccine approach based on the use of the whole microorganism could not be applied for GAS vaccine development due to the risk of induction of autoimmune responses. Peptide-based subunit vaccine are fully defined, safer and can avoid triggering autoimmune responses by  accurate choice of a minimal antigen2. However, peptide antigens are poor immunogens and require the use of an appropriate delivery system/adjuvant to produce effective peptide-based vaccines3. Liposomes have been considered as an attractive vaccine delivery systems are biocompatible, biodegradable and low toxic and have the capability of carrying both hydrophilic and hydrophobic molecules4. In addition, cell-penetrating peptides (CPPs) as delivery enhancers have been widely used in DNA vaccine delivery systems5 since they have the capacity of facilitating antigen translocation through cell membrane.

In the present study, we designed a novel peptide-based vaccine against GAS by combining (a) lipid core peptides (LCP) self-adjuvanting system, which consisted of J8 GAS-derived antigenic peptide, branching lysine and lipopeptide adjuvant moiety, with (b) liposomal delivery system5.  In addition, CPPTat, as the most extensively studied CPP in vaccine delivery, was anchored via a variety of linker to the surface of above liposomes. We evaluated ability to induce immune responses of different Tat derivatives in above liposomal peptide-based vaccine and showed that CPP-liposomes could be considered as a promising delivery against GAS.

  1. 1. Good, M.F., Pandey, M., Batzloff, M.R. and Tyrrell, G.J., 2015. Strategic development of the conserved region of the M protein and other candidates as vaccines to prevent infection with group A streptococci. Expert review of vaccines, 14(11), pp.1459-1470.
  2. 2. Skwarczynski, M. and Toth, I., 2016. Peptide-based synthetic vaccines. Chemical Science, 7(2), pp.842-854.
  3. 3. Skwarczynski, M. and Toth, I., 2011. Peptide-based subunit nanovaccines. Current drug delivery, 8(3), pp.282-289.
  4. 4. Park, J.W., 2002. Liposome-based drug delivery in breast cancer treatment. Breast Cancer Research, 4(3), p.95.
  5. 5. Ghaffar, K.A., Marasini, N., Giddam, A.K., Batzloff, M.R., Good, M.F., Skwarczynski, M. and Toth, I., 2016. Liposome-based intranasal delivery of lipopeptide vaccine candidates against group A streptococcus. Acta biomaterialia, 41, pp.161-168.