BACKGROUND:
Rheumatic heart disease (RHD) is a chronic non-communicable cardiovascular disease resulting from dysregulated immune responses following an initial Group A Streptococcus (Strep A) infection. Although Strep A exposure is common, progression to RHD occurs in only a subset of individuals, suggesting that antigen-specific immune recognition plays a central role in disease pathogenesis (1, 2). This study sought to establish a human immune-guided antigen discovery platform, to interrogate immunodominant Strep A antigens with potential relevance to immune-mediated mechanisms underlying RHD.

METHODS:
Intravenous immunoglobulin (IVIG) was utilised as a population-level archive of human polyclonal immune memory, reflecting the cumulative natural exposure to Strep A. Polyclonal IgG was immobilised onto activated chromatography resin serving as an affinity matrix for selective antigen–antibody binding. Incubation with protein extracts from highly prevalent Strep A enabled enrichment of Strep A-specific proteins. Eluted proteins will be subjected to proteomic analysis to identify immunodominant Strep A antigens (3). Expected Impact: We have utilised a phased approach to identify Strep A antigens most frequently recognised by human immunity rather than selected solely by pathogen abundance. This platform provides a framework to prioritise antigen-specific immune targets that may contribute to the transition from acute Strep A infection to chronic non-communicable cardiac disease. This work lays the foundation for rational immune-based preventive strategies, including the development of interventions aimed at reducing the global burden of RHD.