Oral Presentation Lancefield International Symposium for Streptococci and Streptococcal Diseases 2025

The development of early life natural immunity to Streptococcus pyogenes: focus on conserved vaccine antigens in a high burden setting (117017)

Alexander J Keeley 1 2 3 , Fatoumata E Camara 2 , Edwin Armitage 2 , Gabrielle de Crombrugghe 4 , Jainaba Sillah 2 , Victoria Rollinson 2 , Modou Lamin Fofana 2 , Elina Senghore 2 , Musokoi Jammeh 2 , Alana L Whitcombe 5 , Amat Bittaye 2 , Haddy Cessay 2 , Isatou Cessay 2 , Bunja Samateh 2 , Muhammed Manneh 2 , Martina Carducci 6 , Luisa Massai 6 , Danilo Moriel Gomes 6 , Adam Kucharski 1 , Pierre Smeesters 4 , Anne Botteaux 4 , Ya Jankey Jayne 2 , Nicole J Moreland 5 , Ed Clarke 2 , Beate Kampmann 2 7 , Michael Marks 1 , Omar Rossi 6 , Henrick Salje 8 , Claire E Turner 9 , Thushan I de Silva 2 3
  1. London School of Hygiene & Tropical Medicine, London, LONDON, United Kingdom
  2. Vaccines and Immunity, MRC Unit The Gambia at LSHTM, Fajara, The Gambia
  3. Division of Clinical Medicine, University of Sheffield, Sheffield, UK
  4. Molecular Bacteriology Laboratory, Université Libre de Bruxelles, Brussels, Belgium
  5. Faculty of Medical and Health Sciences, , The University of Auckland, Auckland, New Zealand
  6. GSK Vaccines Institute for Global Health (GVGH), Siena, Italy
  7. Charité Centre for Global Health, Berlin, Germany
  8. Department of Genetics, University of Cambridge, Cambridge, UK.
  9. School of Biosciences, University of Sheffield, Sheffield, United Kingdom

Background

Understanding the natural development of immunity to Streptococcus pyogenes is essential for vaccine design, particularly in high-burden settings. Conserved antigens SpyCEP, SLO, SpyAD, and GAC are key vaccine candidates, but their role in protection remains underexplored.

 

Methods

IgG levels to conserved vaccine antigens and DNAseB were measured on a Luminex multiplex assay from 620 participants in two longitudinal cohorts in The Gambia1,2. Maternal IgG transfer, and longitudinal dynamics were assessed, alongside associations between IgG levels and protection from culture-confirmed S. pyogenes events.

 

Results

Maternal IgG to conserved antigens was efficiently transferred at birth, but levels waned rapidly during infancy. By 11 months, 23% of infants showed serological evidence of S. pyogenes exposure. IgG to conserved antigens rose rapidly in early childhood, driven by exposure. Following culture-confirmed events, absolute IgG increased were greatest in under 2s, regardless of the event site or presence of symptoms. From IgG measured at 1987 timepoints, reduced odds of S. pyogenes events within 45 days were associated with higher IgG levels to SLO (0.06, 0.01- 0.49), SpyAD (0.34,0.15-0.77) and SpyCEP (0.25,0.09-0.68). Putative 50% protective thresholds were defined as 35,740 RLU/mL for SLO, 60,346 RLU/mL for SpyAD, and 62,210 RLU/mL for SpyCEP.

 

Discussion

Our findings provide evidence of protection associated with IgG to conserved vaccine antigens in a high-burden setting. These results, which require validation in clinical vaccine trials or human challenge studies, suggest early life serological responses are driven by intense exposure, support conserved vaccine strategies and inform future efforts to optimize immunization schedules.

  1. Armitage, E. P. et al. Streptococcus pyogenes carriage and infection within households in The Gambia: a longitudinal cohort study. Lancet Microbe 5, 679–688 (2024).
  2. Keeley, A. J. et al. Development and Characterisation of a Four-Plex Assay to Measure Streptococcus pyogenes Antigen-Specific IgG in Human Sera. Methods Protoc. 5, 55 (2022).