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Mucosal Immune Responses to Streptococcus pyogenes across the Life Course in a High Burden Setting: A Focus on Candidate Vaccine Antigens

par Camara, Fatoumata E.;De Crombrugghe De Looringhe, Gabrielle ; [et al.]
Référence SSRN Electronic Journal
Publication Publié, 2025-10-02

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Résumé :

Background: Streptococcus pyogenes causes half a million deaths each year, yet limited understanding of natural mucosal immunity, particularly from high burden settings, impedes progress towards a safe and effective vaccine. Limited human data suggest a role for IgA mediated mucosal immunity in protection. We aimed to describe the evolution of mucosal IgA responses to candidate vaccine antigens across the life course, and explore their association with protection from S. pyogenes carriage and disease, from an intensively sampled household longitudinal cohort study in The Gambia. Methods: We developed and characterised a Luminex assay to measure IgA to vaccine antigens GAC, SLO, SpyAD and SpyCEP in oral fluid samples collected from a longitudinal cohort study in The Gambia. Assay specificity, linearity and reproducibility were characterised. IgA was measured from 1504 samples; at study baseline, and around culture confirmed events in cases and household controls. Mixed effects logistic regression was used to explore the association between IgA levels to each antigen and the risk of any culture confirmed event within 45 days. Findings: There was evidence of compartmentalisation of IgA responses, compared to blood IgG, with limited correlation between compartments for each antigen in baseline samples; Pearson’s correlation coeffecients ranging from 0.36 for GAC to 0.43 for SpyAD. Protection from any culture-confirmed event within the next 45 days was associated with higher IgA levels in oral fluid to SpyCEP (odd ratio (OR) 0.58, 95% confidence interval (CI) 0.38-0.89, p=0.013) and SpyAD (OR 0.6, CI 0.4-0.91, p= 0.015). Interpretation: IgA may play a role in attenuating S. pyogenes at the mucosal surface, reducing carriage and disease and limiting systemic serological responses following exposure. These findings suggest that vaccines which induce protective mucosal immune responses against S. pyogenes should be evaluated.