Background: Group A Streptococcus (Strep A) is a globally significant pathogen responsible for over 775 million infections and 600,000 annual deaths. At the core lies the common "strep throat" infection, which often results in hospital visits and can lead to serious health complications such as sepsis, meningitis, "flesh-eating disease," and severe life-threatening conditions such as rheumatic heart disease. The global burden of Strep A diseases disproportionately affects vulnerable and marginalised communities. In Australia, this disparity is particularly over-represented among young Aboriginal and Torres Strait Islander individuals, highlighting a major health crisis driven by a lack of health equity. Strep A is an upper respiratory pathogen, and therefore mucosal immunity is likely required to prevent infections. The current Strep A vaccine landscape is limited, and the few vaccine candidates are designed to elicit a systemic immune response. However, developing a vaccine capable of eliciting an immune response at mucosal surfaces is critically important, yet mucosal vaccines for Strep A have been under-explored. There is a critical need for greater understanding of mucosal immune responses that are protective and longer lasting, to inform next-generation vaccine strategies. Methods: Here, we explore and characterise prospective mucosal vaccine candidates in unique cohorts of pharyngitis samples using discovery-based approaches. Results/Conclusion: This technology will be used to guide vaccine development through a comprehensive view of protein changes that occur in response to infection and by comparing protein profiles between symptomatic and asymptomatic individuals. This knowledge will fuel the design of superior next-generation vaccine strategies against Strep A.