Immunization with a tetraepitopic lipid core peptide vaccine construct induces broadly protective immune responses against group A streptococcus.
BACKGROUND
The development of a vaccine to prevent infection with group A streptococcus (GAS) is hampered by the widespread diversity of circulating GAS strains and M protein types, and it is widely believed that a multivalent vaccine would provide better protective immunity.


METHODS
We investigated the efficacy of incorporating 3 M protein serotypic amino-terminal epitopes from GAS isolates that are common in Australian Aboriginal communities and a conformational epitope from the conserved carboxy-terminal C-repeat region into a single synthetic lipid core peptide (LCP) vaccine construct in inducing broadly protective immune responses against GAS after parenteral delivery to mice.


RESULTS
Immunization with the tetraepitopic LCP vaccine construct led to high titers of systemic, antigen-specific IgG responses and the induction of broadly protective immune responses, as was demonstrated by the ability of immune serum to opsonize multiple GAS strains. Systemic challenge of mice with a lethal dose of GAS given 60 or 300 days after primary immunization showed that, compared with the control mice, the vaccinated mice were significantly protected against GAS infection, demonstrating that the vaccination stimulated long-lasting protective immunity.


CONCLUSIONS
These data support the efficacy of the LCP vaccine delivery system in the development of a synthetic, multiepitopic vaccine for the prevention of GAS infection.
Olive
Colleen
C
Cooperative Research Centre for Vaccine Technology, Queensland Institute of Medical Research, Brisbane, Australia. colleenO@qimr.edu.au
Ho
Mei-Fong
MF
Dyer
Joanne
J
Lincoln
Douglas
D
Barozzi
Nadia
N
Toth
Istvan
I
Good
Michael F
MF
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D008055:Lipids / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D009895:Opsonin Proteins / Q000097:blood; D013290:Streptococcal Infections / Q000276:immunology / Q000517:prevention & control*; D022541:Streptococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000276:immunology*; D016019:Survival Analysis; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D000939:Epitopes; D007074:Immunoglobulin G; D008055:Lipids; D009895:Opsonin Proteins; D022541:Streptococcal Vaccines; D022223:Vaccines, Subunit; C014689:streptococcal M protein