Currently there is no commercial Group A Streptococcus (GAS; S. pyogenes) vaccine available. The development of safe GAS vaccines is challenging, researchers are confronted with obstacles such as the occurrence of many unique serotypes (there are greater than 150 M types), antigenic variation within the same serotype, large variations in the geographical distribution of serotypes, and the production of antibodies cross-reactive with human tissue which can lead to host auto-immune disease. Cell wall anchored, cell membrane associated, secreted and anchorless proteins have all been targeted as GAS vaccine candidates. As GAS is an exclusively human pathogen, the quest for an efficacious vaccine is further complicated by the lack of an animal model which mimics human disease and can be consistently and reproducibly colonized by multiple GAS strains.