The preferred product characteristics for a Group A Streptococcus (GAS) vaccine, as outlined by the World Health Organization, recommend effective protection against pharyngitis as a relevant and feasible goal for early phase clinical development. The non-human primate (NHP) model of GAS pharyngitis has been used to investigate vaccine immunogenicity and efficacy. Whilst opsonophagocytic killing (OPK) has been suggested as a potential correlate of protection for M protein-based vaccines, factors that provide protective efficacy for non-M protein vaccines are not defined. Here, we explore efficacy, OPK and antigen neutralization using the NHP pharyngitis model to compare preclinical GAS vaccine Combo#5 antigens formulated with either aluminium hydroxide (Alum) the SMQ adjuvent. SMQ is a squalene-in-water emulsion containing the saponin QS21 and the synthetic toll-like receptor 4 ligand 3D(6-acyl)-PHAD®, which elicits a more balanced Th1/Th2-type immune response compared with aluminium hydroxide. Vaccination of NHPs with Combo#5-SMQ resulted in reduced GAS colonization whereas vaccination with Combo#5-Alum did not. Both Alum-adjuvanted and SMQ-adjuvanted vaccines generated high antibody titers against all five Combo#5 antigens. Neither vaccine generated detectable OPK titers. Both vaccines generated comparable functional inhibition of streptolysin O and Streptococcus pyogenes cell envelope IL8 protease (SpyCEP). These findings suggest that correlates of protection afforded by the Combo#5-SMQ vaccine formulation may be represented by differences in functional inhibition of other Combo#5 antigens or other immunological parameters.