Streptococcus pyogenes (group A streptococcus, GAS) is an important human pathogen that is responsible for a range of diseases. Non-invasive diseases include pharyngitis, scarlet fever and pyoderma/impetigo. GAS is also capable of causing invasive diseases such as streptococcal toxic shock syndrome and necrotizing fasciitis. There is a high chance of mortality associated with GAS invasive diseases, with approximately 8-23% of patients dying within 7 days of infection. Consecutive GAS infections may give rise to auto-immune complications, including acute rheumatic fever (ARF) and rheumatic heart disease (RHD). Approximately 2-3% of patients who acquire streptococcal pharyngitis develop ARF. Skin-associated GAS strains have also been linked to cases of ARF. A vaccine that can stop the progression of disease from the primary sites of infection (URT and skin) is desperately needed.