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.