Streptococcus pyogenes, or Group A Streptococcus (GAS) is responsible for significant patient morbidity and mortality in the developing world and within the Australian Indigenous population. GAS is responsible for a variety of diseases such as invasive necrotizing fasciitis and toxic shock syndrome, as well as non-invasive diseases, such as pharyngitis, impetigo, scarlet fever and otitis media. However, GAS sequelae such as rheumatic fever and rheumatic heart disease are responsible for the highest morbidity. The 30-valent vaccine candidate currently
in trials is inappropriately specialised to serotypes present in areas with low GAS incidence, such as the United States.
The difficulty in creation of a suitable vaccine lies in part with the variety of GAS virulence factors. The M protein is a highly abundant, multifunctional immunogenic surface protein which confers resistance to phagocytes and complement mediated protection. As sections of the M
protein is highly conserved, it has been the focus of vaccination research. Furthermore, protein fragments J8 and J14 within the M protein have given encouraging results within a mouse model.
Virus-like particle (VLP) technology offers a promising alternative to existing vaccination delivery systems. VLPs are able to induce both cell mediated and humoral immune responses. In this study, the use of a chimeric hepatitis B surface antigen VLP expressing M
protein epitopes p145, J8 and J14 for use as a dual vaccine against Hepatitis B virus (HBV) and GAS is investigated. Specifically, PCR generated DNA sequences of J8, J14 and p145 from the M protein of GAS have been cloned into the highly immunogenic ‘a’ determinant region of the HBsAg-S VLP and transformed into human embryonic kidney (HEK293T) cells. Expressed recombinant HBsAg-S-GAS-m protein constructs were assayed by ELISA to confirm presentation of GAS epitopes. ELISA results showing high titres were obtained for VLP:p145 but low titres were obtained for VLP:J8 and VLP:J14. Further sequencing of plasmid constructs, protein expression and antigenic screening of proteins is required before the study can progress to proof-of-concept murine challenge models
