Streptococcus pyogenes (Group A Strep; Strep A) is a significant human pathogen, primarily infecting skin and pharynx. A broader understanding of the role of bacterial and host factors within the oropharyngeal niche is needed to inform new therapeutic strategies. Experimental human infection with emm75 S. pyogenes (CHIVAS M75 study) allows for the detection of novel correlates of protection or infection in the oropharyngeal environment. Using a time-course approach, we are characterising the dynamic glycome and proteome in saliva following pharyngeal challenge with Strep A in human participants. Baseline, acute, and convalescent saliva samples were collected from healthy adult participants challenged with emm75 S. pyogenes. Qualitative and quantitative analyses of N-glycans extracted from saliva was performed by liquid chromatography coupled with mass spectrometry (PGC-LC-ESI-MS/MS; LC-MS). Analyses of the salivary proteome are also conducted using LC-MS in a shotgun proteomics approach. Of 145 N-glycans detected in the saliva of one participant, 108 have been structurally solved or predicted from elution profiles and MS2 analyses. The majority (60%) are complex N-glycans. A major change detected is an increase in N-glycans bearing neuraminic (sialic) acid, which has a well-recognised role in the innate immune response. Analyses of the proteome and glycoproteome are underway to map observed glycan changes to specific salivary proteins. The host glycome and proteome are important research targets for efforts to understand host-pathogen interactions in streptococcal pharyngitis, and these findings will be validated in a larger cohort of human challenge trial participants. The observed sialic acid response suggests it may have an important role in triggering innate immune responses to S. pyogenes mucosal infections.