title: Protection of mice from group A streptococcal infection by intranasal immunisation with a peptide vaccine that contains a conserved M protein B cell epitope and lacks a T cell autoepitope.
abstract: Infection with group A streptococci (GAS) can lead to rheumatic fever (RF) and rheumatic heart disease (RHD) which are a major health concern particularly in indigenous populations worldwide, and especially in Australian Aboriginals. A primary route of GAS infection is via the upper respiratory tract, and therefore, a major goal of research is the development of a mucosal-based GAS vaccine. The majority of the research to date has focused on the GAS M protein since immunity to GAS is mediated by M protein type-specific opsonic antibodies. There are two major impediments to the development of a vaccine-the variability in M proteins and the potential for the induction of an autoimmune response. To develop a safe and broad-based vaccine, we have therefore focused on the GAS M protein conserved C-region, and have identified peptides, J8 and the closely related J8 peptide (J14), which may be important in protective immunity to GAS infection. Using a mucosal animal model system, our data have shown a high degree of throat GAS colonisation in B10.BR mice 24h following intranasal immunisation with the mucosal adjuvant, cholera toxin B subunit (CTB), and/or diptheria toxoid (dT) carrier, or PBS alone, and challenge with the M1 GAS strain. However, GAS colonisation of the throat was significantly reduced following intranasal immunisation of mice with the vaccine candidate J8 conjugated to dT or J14-dT when administered with CTB. Moreover, J8-dT/CTB and J14-dT/CTB-immunised mice had a significantly higher survival when compared to CTB and PBS-immunised control mice. These data indicate that immunity to GAS infection can be evoked by intranasal immunisation with a GAS M protein C-region peptide vaccine that contains a protective B cell epitope and lacks a T cell autoepitope.
authors.affiliation: Cooperative Research Centre for Vaccine Technology, The Queensland Institute of Medical Research, PO Royal Brisbane Hospital, Brisbane, QLD 4029, Australia. colleenO@qimr.edu.au
authors.forename: Colleen
authors.initials: C
authors.lastname: Olive
authors.forename: Timothy
authors.initials: T
authors.lastname: Clair
authors.forename: Penny
authors.initials: P
authors.lastname: Yarwood
authors.forename: Michael F
authors.initials: MF
authors.lastname: Good
mesh_terms: D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology*; D017124:Conserved Sequence / Q000276:immunology; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006801:Humans; D007114:Immunization; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D051379:Mice; D008969:Molecular Sequence Data; D010614:Pharynx / Q000382:microbiology; D013290:Streptococcal Infections / Q000517:prevention & control*; D022541:Streptococcal Vaccines / Q000276:immunology*; D013297:Streptococcus pyogenes / Q000254:growth & development / Q000276:immunology*; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D022541:Streptococcal Vaccines; D022223:Vaccines, Subunit; C014689:streptococcal M protein