This study demonstrates the effectiveness of a novel self-adjuvanting
vaccine delivery system for multiple different synthetic
peptide immunogens by use of
lipid core
peptide (LCP) technology. An LCP formulation incorporating two different protective
epitopes of the surface antiphagocytic M
protein of group A streptococci (GAS)--the causative agents of
rheumatic fever and subsequent
rheumatic heart disease--was tested in a murine parenteral immunization and GAS challenge model. Mice were immunized with the LCP-GAS formulation, which contains an M
protein amino-terminal type-specific
peptide sequence (8830) in combination with a conserved non-host-cross-reactive carboxy-terminal C-region
peptide sequence (
J8) of the M
protein. Our data demonstrated immunogenicity of the LCP-8830-J8 formulation in B10.BR mice when coadministered in complete
Freund's adjuvant and in the absence of a conventional adjuvant. In both cases, immunization led to induction of high-titer GAS
peptide-specific serum
immunoglobulin G antibody responses and induction of highly opsonic
antibodies that did not cross-react with human heart tissue
proteins. Moreover, mice were completely protected from GAS
infection when immunized with LCP-8830-J8 in the presence or absence of a conventional adjuvant. Mice were not protected, however, following immunization with an LCP formulation containing a control
peptide from a Schistosoma sp. These data support the potential of LCP technology in the development of novel self-adjuvanting multi-
antigen component
vaccines and point to the potential application of this system in the development of human
vaccines against
infectious diseases.