Intranasal administration is an effective mucosal vaccine delivery route for self-adjuvanting lipid core peptides targeting the group A streptococcal M protein.
BACKGROUND
We investigated the lipid core peptide (LCP) system for mucosal vaccine delivery against infection with group A streptococcus (GAS)--the causative pathogen of rheumatic fever and rheumatic heart disease.


METHODS
An LCP vaccine formulation containing 2 different peptide epitopes of the antiphagocytic M protein of GAS--a conformational epitope from the carboxyterminal conserved C-repeat region and an aminoterminal serotypic epitope--was intranasally administered to mice with cholera toxin B subunit or without additional adjuvant.


RESULTS
Our data demonstrate that the LCP vaccine formulation induced the elicitation of antigen-specific systemic immunoglobulin G responses when administered with or without cholera toxin B subunit, whereas cholera toxin B subunit was required for the induction of antigen-specific mucosal immunoglobulin A responses. Immune serum samples from vaccinated mice were capable of opsonization of a homologous GAS strain, as well as opsonization of a heterologous GAS strain. Furthermore, mice were protected from GAS challenge following immunization with the LCP vaccine formulation, even in the absence of additional adjuvant.


CONCLUSIONS
These data support the potential of the LCP system in the development of a self-adjuvanting, synthetic, peptide-based mucosal GAS vaccine for the prevention of diseases caused by GAS.
Olive
Colleen
C
Cooperative Research Centre for Vaccine Technology, The Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Brisbane, Queensland 4029, Australia. colleenO@qimr.edu.au
Sun
Hsien Kuo
HK
Ho
Mei-Fong
MF
Dyer
Joanne
J
Horváth
Aniko
A
Toth
Istvan
I
Good
Michael F
MF
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000284:Administration, Oral; D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D004168:Diphtheria Toxoid / Q000008:administration & dosage / Q000276:immunology; D016503:Drug Delivery Systems / Q000379:methods; D000939:Epitopes / Q000276:immunology; D018928:Immunity, Mucosal / Q000276:immunology; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D016233:Immunotherapy, Active / Q000379:methods*; D008055:Lipids / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology*; D013290:Streptococcal Infections / Q000276:immunology / Q000517:prevention & control; D022541:Streptococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology; D013297:Streptococcus pyogenes / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage* / Q000276:immunology
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D004168:Diphtheria Toxoid; D000939:Epitopes; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008055:Lipids; D010446:Peptide Fragments; D022541:Streptococcal Vaccines; D022223:Vaccines, Subunit; C014689:streptococcal M protein