Introduction: Longitudinal cohort studies provide insights into immune responses to Streptococcus pyogenes (Strep A) and support vaccine development by providing baseline data to inform trial design. Electrochemiluminescent multiplexed assays on the Mesoscale Discovery (MSD) platform enable high-throughput measurement of antibodies to multiple antigens with high sensitivity, minimal sample volume, and broad dynamic range. This is the first longitudinal cohort study in children to apply the Strep A 6-plex MSD assay to evaluate immune responses to Strep A pharyngitis.
Methods: The ASAVI urban pharyngitis surveillance study enrolled 476 children aged 3-14 years for 12-months and followed them for episodes of sore throat and periodically when healthy. Blood samples were collected at baseline, 3-5 weeks post Strep A sore throat episodes, and every 4-6 months (seasonal visits.) The Strep A 6-plex assay measured IgG responses to SpyCEP, DNase B, SLO, SpyAD, C5a peptidease, and group A carbohydrate (GAC).
Results: Of 692 samples tested, 123 were from participants with Strep A point-of-care test positive sore throats. Baseline antibody levels increased with age, indicating cumulative exposure over time. Antigen-specific IgG levels increased following a Strep A-positive sore throat and individual variability was observed. Findings highlight the expected variability in the natural immune response in exposed individuals and provide insight into the immune response to six Strep A antigens.
Conclusion: Our results provide insights into immune responses associated with natural infection and colonisation, and provide a foundation for evaluating immunogenicity of vaccine antigens using the MSD platform for clinical studies and vaccine trials.