Potential of lipid core peptide technology as a novel self-adjuvanting vaccine delivery system for multiple different synthetic peptide immunogens.

Abstract

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.

• Authors: Colleen Olive, Michael Batzloff, Aniko Horváth, Timothy Clair, Penny Yarwood, Istvan Toth, Michael F Good
• Journal: Infection and immunity (Infect Immun) Vol. 71 Issue 5 Pg. 2373-83 (May 2003) ISSN: 0019-9567 [Print] United States
• PMID: 12704107 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Bacterial
• Antigens, Bacterial
• Bacterial Outer Membrane Proteins
• Carrier Proteins
• Immunoglobulin G
• Lipids
• Peptide Fragments
• Streptococcal Vaccines
• Vaccines, Synthetic
• streptococcal M protein

Topics

• Amino Acid Sequence
• Animals
• Antibodies, Bacterial (blood)
• Antigens, Bacterial
• Bacterial Outer Membrane Proteins (immunology)
• Carrier Proteins (immunology)
• Cross Reactions
• Drug Delivery Systems
• Female
• Immunoglobulin G (blood, classification)
• Lipids
• Mice
• Molecular Sequence Data
• Peptide Fragments (immunology)
• Phagocytosis
• Streptococcal Vaccines (administration & dosage, immunology)
• Streptococcus pyogenes (immunology)
• Vaccines, Synthetic (administration & dosage)