Professor The University of Queensland, St. Lucia, Queensland, Australia
Infection with group A streptococci (Streptococcus pyogenes, GAS), one of the common and widespread human pathogens, can result in a broad range of diseases, with the potential of acute and post-infectious rheumatic fever and rheumatic heart disease. Immunity to GAS relies on the production of opsonic antibodies specific to the hypervariable N-terminal and conserved C-terminal regions of the coiled-coil α-helical M protein, the major virulent factor in GAS. The development of an effective vaccine for GAS has been challenged by the induced autoimmunity of epitopes derived from the C-terminal regions, unsuitable B-cell epitopes that have been shown to react with human heart tissue, and the minimal B-cell epitopes, which believed to be safe, shows little or no immunogenicity unless bound to a delivery platform. For vaccine delivery, self-adjuvanting lipid core peptide (LCP) and polymer coated liposome systems including antigen, carrier and adjuvant within the same molecular entity has been developed. The systems allow the attachment of multiple copies of antigens.
We synthesized a dendritic structure (LCP) consisting of a lipoamino acids, polylysine carrier and a peripheral generation of the minimal B-cell epitope (J14) and CD4+ T helper cell epitope (P25). The peptide dendritic core and the epitopes were synthesized using solid phase peptide synthesis. Blank liposomes which contained the LCP were formulated and optimized for charge and lipid content using a thin film formation method. Optimized liposomes were coated with positively charged trimethyl chitosan (TMC) then negatively charged sodium alginate in a layer-by-layer approach. These formulations were subsequently characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Optimized formulations were further investigated for their efficiency of uptake by intestinal immune cells and ability to induce mucosal IgA and systemic IgG responses after oral administration.