Group A streptococcal vaccine delivery by immunization with a self-adjuvanting M protein-based lipid core peptide construct.
OBJECTIVE
To develop a broad strain coverage GAS vaccine, several strategies have been investigated which included multi-epitope approaches as well as targeting the M protein conserved Cregion. These approaches, however, have relied on the use of adjuvants that are toxic for human application. The development of safe and effective adjuvants for human use is a key issue in the development of effective vaccines. In this study, we investigated the lipid polylysine core peptide (LCP) system as a self-adjuvanting GAS vaccine delivery approach.


METHODS
An LCP-GAS construct was synthesised incorporating multiple copies of a protective peptide epitope (J8) from the conserved carboxy terminal C-repeat region of the M protein. B10.BR mice were immunized parenterally with the LCP-J8 construct, with or without conventional adjuvant, prior to the assessment of immunogenicity and the induction of serum opsonic antibodies.


RESULTS
Our data demonstrated immunogenicity of LCP-J8 when coadministered in complete Freund's adjuvant (CFA), or administered in the absence of conventional adjuvant. In both cases, immunization led to the induction of high-titre J8 peptide-specific serum IgG antibody responses, and the induction of heterologous opsonic antibodies that did not cross-react with human heart tissue proteins.


CONCLUSIONS
These data indicated the potential of a novel self-adjuvanting LCP vaccine delivery system incorporating a synthetic GAS M protein C-region peptide immunogen in the induction of broadly protective immune responses, and pointed to the potential application of this system in human vaccine development against infectious diseases.
Olive
Colleen
C
Cooperative Research Centre for Vaccine Technology, The Queensland Institute of Medical Research PO Royal Brisbane Hospital, University of Queensland, Brisbane Queensland, 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; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001426:Bacterial Proteins / Q000737:chemistry*; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D008055:Lipids / Q000737:chemistry*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry*; D013291:Streptococcus / Q000276:immunology*
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D008055:Lipids; D010455:Peptides