Potential of lipid core peptide technology as a novel self-adjuvanting vaccine delivery system for multiple different synthetic peptide immunogens.
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.
Olive
Colleen
C
Cooperative Research Centre for Vaccine Technology, Division of Infectious Diseases and Immunology, The Queensland Institute of Medical Research, Brisbane, Queensland 4029, Australia. colleenO@qimr.edu.au
Batzloff
Michael
M
Horváth
Aniko
A
Clair
Timothy
T
Yarwood
Penny
P
Toth
Istvan
I
Good
Michael F
MF
D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D003429:Cross Reactions; D016503:Drug Delivery Systems; D005260:Female; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D008055:Lipids; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D010587:Phagocytosis; D022541:Streptococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology; D013297:Streptococcus pyogenes / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D007074:Immunoglobulin G; D008055:Lipids; D010446:Peptide Fragments; D022541:Streptococcal Vaccines; D014614:Vaccines, Synthetic; C014689:streptococcal M protein