Group A Streptococcus (GAS) is an important human pathogen responsible for superficial infections of the skin and throat and serious invasive infections including necrotizing fasciitis and streptococcal toxic shock syndrome. Repeated mild infections can also lead to long-term autoimmune complications. Disease and economic burden data support the rationale for the development of a vaccine against GAS. One of the several hurdles in GAS vaccine development is the variability of protection observed in different animal models, particularly in mice. We have used a non-human primate (NHP) model for pharyngeal infection to assess GAS vaccine protective efficacy. The NHP model was validated using full-M1 protein as a vaccine antigen and used to evaluate the protective efficacy of an experimental vaccine (Combo#5) containing streptolysin O, IL-8 protease, C5a peptidase, arginine deiminase and trigger factor. All antigens were adjuvanted with Alum and NHPs were immunised via intramuscular injection on weeks 0, 8 and 17. On week 20, NHPs were challenged with M1T1 GAS strain 5448 via intranasal delivery. High-titre antigen-specific antibody responses were detected in NHP serum samples against all antigens and immunised NHPs showed a reduction in pharyngitis and tonsillitis symptoms compared to control NHPs. This work demonstrates the protective efficacy of a non-M protein combination vaccine in a NHP model of pharyngitis and tonsillitis.