Background: The antigenic heterogeneity of GAS poses a challenge for vaccine design. The age-based incidence of GAS infection—peaking in childhood and lowering 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 an 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.
Author Contributions
Conceptualization, D.E.B.; formal analysis, D.E.B., L.K., S.H.L. and J.M.D.; investigation, J.M.D., F.F.T., S.B., A.S., S.K. and J.H.L.; funding acquisition, D.E.B. All authors have read and agreed to the published version of the manuscript.
Funding
This research was funded by the National Institutes of Health, grant number R01AI173565.
Institutional Review Board Statement
The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board of New York Medical College (protocol code 15887 on 22 August 2022).
Informed Consent Statement
Informed consent was obtained from all subjects involved in the initial blood collection study; the work reported here was deemed exempt: (4) Secondary Research Uses of Data or Specimens.
Data Availability Statement
This is a conference abstract based on preliminary findings and analysis of data from an ongoing study.
Conflicts of Interest
The authors declare no conflict of interest.
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