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.