Lipopeptide Nanoparticulate Vaccine Candidates for the Induction of Protective Immune Responses

The development of an effective vaccine for group A streptococci (GAS) has been challenged by the induced autoimmunity of epitopes derived from the C-repeat regions. Additionally, there are B-cell epitopes that have been shown to react with human heart tissue. Shorter safe B-cell epitopes, show little or no immunogenicity unless bound to a delivery platform including the conjugation to an inbuilt adjuvant. Self-adjuvanting lipid core peptide (LCP) systems where the antigen(s), carrier and adjuvant were within the same molecular entity has been developed. The LCP amphiphilic construct was incorporated into liposomes to produce particles with the desired size. The construct alone elicited high-levels of antibody titers comparable to that of the positive control (J8 + Complete Freund’s adjuvant). The developed strategy to produce nanoparticles, consisting of a peripheral antigenic epitope layer conjugated to a dendrimer core, which is both self-adjuvanting and produces a strong immune response to the GAS M-protein, offers an attractive alternative to conventional vaccine approaches. The greatest advantage of this system being the generation of protective immune response after oral administration. Our dendrimer-nanoparticles vaccine approach should be readily acquiescent to other pathogenic organisms in addition to GAS, and may prove particularly useful for the design of vaccines against infection deceases know to stimulate autoimmune response in a host.