Oral Presentation Lancefield International Symposium for Streptococci and Streptococcal Diseases 2025

Exploring mucosal humoral immunity to Streptococcus pyogenes in oral fluid within a longitudinal household cohort study in The Gambia. (118029)

Fatoumata Camara 1 2 , Alexander Keeley 2 3 , Edwin Armitage 2 , Gabrielle De Crombrugghe 2 4 , Alana L Whitcombe 5 , Jainaba Sillah 2 , Modou Lamin Fofana 2 , Elina senghore 2 , Musukoi Jammeh 2 , Muhammed Manneh 2 , Haddy Ceesay 2 , Isatou Ceesay 2 , Amat Bittaye 2 , Bunja Samateh 2 , Martina Carducci 6 , Danilo Moriel Gomes 6 , Adam Kucharski 2 , Pierre Smeesters 4 , Ya Jankey Jagne 2 , Nicole J Moreland 5 , Ed Clarke 2 , Beate Kampmann 2 , Micheal Marks 2 , Omar Rossi 6 , Henrik Salje 3 , Claire Turner 3 , Thushan de Silva 2 3
  1. University of Western Australia, Crawley, Perth, WA, Australia
  2. Vaccines and Immunity, Medical Research Council, The Gambia at London School of Hygiene and Tropical Medicine, Fajara, Gambia
  3. University of Sheffield, Sheffield, United Kingdom
  4. Université libre de Bruxelles , Brussels
  5. University of Auckland, Auckland, New Zealand
  6. GSK Vaccines Institute for Global Health., Siena, Italy

Background

Streptococcus pyogenes poses a major global health threat, especially in low- and middle-income countries yet large gaps in understanding natural immunity especially at mucosal level hinder progress towards a vaccine.

Methods

This study utilizes oral fluid samples from a one-year longitudinal cohort in The Gambia  with 442 participants across 44 households. We developed and characterised a Luminex assay to measure IgA and IgG titers to five conserved Strep A antigens (SLO, SpyCEP, DNAse B, SpyAD, and GAC) in oral fluid, comparing to blood IgG measurements.

Results


Oral fluid IgA titres exhibited slower maturation in early life compared to blood and oral fluid IgG. Oral fluid IgA responses from 1262 timepoints with paired oral fluid and blood samples showed evidence of compartmentalisation, with heterogenous response to culture confirmed events and with stronger correlations between IgA level to the different antigens within oral fluid (Pearson’s coefficient 0.56–0.82) compared to cross-compartment correlations (Pearson’s coefficient 0.37–0.42, for each antigen between blood IgG and oral fluid IgA). Reduced odds of culture confirmed Strep A events within 45 days were associated with higher oral fluid IgA titres to SpyCEP (Odds ratio (OR) 0.58, 95% CI 0.38–0.89, p=0.0.13) and SpyAD (HR 0.60, 95% CI 0.40–0.91, p = 0.001).

Conclusions:
These findings highlight oral fluid as a promising non-invasive tool for assessing mucosal immunity to Strep A. Elevated IgA levels to SpyCEP and SpyAD suggest a role for mucosal antibodies in natural protection, supporting their inclusion in candidate vaccines.