Group A Streptococcus (GAS) initially infects humans through mucosal routes such as the throat and skin. Adhesion and colonisation occur in these environments with the potential to lead to mucosal infections and further invasive diseases. Blocking of this interaction at mucosal sites is paramount for an effective GAS vaccine against infections and possible autoimmune sequelae such as rheumatic heart disease (RHD). A study was conducted to compare sublingual (SL) immunisation with subcutaneous (SC) immunisation for induction of systemic and mucosal immunity. BALB/c mice were immunised SL or SC with a combination of protein antigens relevant to several stages of infection (M1 protein; Cpa, pilin protein; SpyCEP, IL-8 protease). IgA and IgG titres were compared in mucosal samples and sera by ELISA. SL delivery was key for mucosal IgA production, but high titres of IgG were generated by both SL and SC immunisation. Responses varied for different antigens, with Cpa showing the highest mucosal IgA response, and SpyCEP the weakest. However, both showed strong systemic IgG production irrespective of immunisation route. The immune response to SL immunisation was dependent on adjuvant. We will present our latest data towards the response to mucosal delivery of vaccines including functional immunity such as neutralisation of IL-8 cleavage by SpyCEP. This study helps to inform thinking towards delivery of GAS vaccines and useful antigens for inclusion to cover all aspects of GAS infection.