Background: The antigenic heterogeneity of GAS poses a challenge for vaccine design. The age-based incidence of GAS infection - peaking in childhood and low by adulthood – is believed to reflect the buildup of protective immunity following repeated infections early in life.

Methods: Serial pediatric serum samples (N > 550) obtained at ~4-month intervals from 86 subjects (USA) were tested for antibody binding to recombinant GAS polypeptides by ELISA.

Results: Type-specific M and T protein antigens (N=14) were tested for binding by serum IgG. Data show ~67 new GAS ‘infections’, as defined by increased IgG immunoreactivity over time. Paired comparisons between pre- and post-infection sera indicate highly significant increases in both ASO and ADB titers (t < 0.005), whereby pre-infection titers were not elevated in ~78% of subjects (<ULN80). Thus, the highly conserved SLO and DNaseB antigens have characteristics expected for the childhood buildup of protective immunity: Low titers pre-infection and high titers post-infection. However, infections by emm pattern A-C throat specialist strains (N=22) showed significant increases for ASO only (t < 0.02), whereas increased ADB is observed with pattern E generalists (N=30; t < 0.05). Ongoing analyses of semi-conserved cell surface proteins derived from the M- and FCT-regions aim to identify antigen combinations that provide protective immunity against the genetically distinct GAS subpopulations.

Conclusions: In a host population where GAS pharyngitis predominates, the pediatric immune response to conserved GAS antigens differs for throat specialist versus generalist strains. Antibody titers pre-infection versus post-infection can guide models for vaccine design.