Poster Presentation Lancefield International Symposium for Streptococci and Streptococcal Diseases 2025

Investigating the role of antibodies to emm type-specific M peptides in natural immunity to Streptococcus pyogenes in The Gambia (#271)

Alexander Keeley 1 2 3 , Fatouamta Camara 3 , Edwin Armitage 3 , Gabrielle de Crombrugghe 4 , Elina Senghore 3 , Musukoi Jammeh 3 , Alana L Whitcombe 3 , Amat Bittaye 3 , Haddy Ceesay 3 , Isatou Ceesay 3 , Bunja Samateh 3 , Muhammed Manneh 3 , Martina Carducci 5 , Chilel Sanyang 3 , Ousman Camara 3 , Ebrima Ceesay 3 , Danilo Moriel Gomes 5 , Pierre Smeesters 6 , Anne Botteaux 6 , Ya Jankey Jayne 3 , Nicole J Moreland 7 , Ed Clarke 3 , Beate Kampmann 3 8 , Michael Marks 1 , Omar Rossi 5 , Henrick Salje 9 , Claire E Turner 10 , Thushan I de Silva 2 3
  1. London School of Hygiene & Tropical Medicine, London, LONDON, United Kingdom
  2. Division of Clinical Medicine, University of Sheffield, Sheffield, UK
  3. Vaccines and Immunity, MRC Unit The Gambia at LSHTM, Fajara, The Gambia
  4. Division of Bacteriology, National Institute for Biological Standards and Control, London, United Kingdom
  5. GSK Vaccines Institute for Global Health (GVGH), Siena, Italy
  6. Molecular Bacteriology Laboratory, Université Libre de Bruxelles, Brussels, Belgium
  7. Faculty of Medical and Health Sciences, , The University of Auckland, Auckland, New Zealand
  8. Charité Centre for Global Health, Berlin, Germany
  9. Department of Genetics, University of Cambridge, Cambridge, UK.
  10. School of Biosciences, University of Sheffield, Sheffield, United Kingdom

Background:

Streptococcal M protein, encoded by the emm gene, is a key virulence factor of Streptococcus pyogenes and the primary target of several vaccine candidates. With over 275 emm-types globally, its diversity poses challenges for vaccine coverage in high-burden like The Gambia.

 

Methods:

IgG levels to 14 M/emm cluster-representative, and 5 additional E3 cluster hypervariable region peptides were measured using a multiplex Luminex assay from two longitudinal Gambian cohorts, including mother/child pairs, and compared to IgG levels to conserved antigens: GAC, SLO, SpyCEP, SpyAD and DNAseB1,2,3. Culture-confirmed S. pyogenes events were emm-typed, allowing assessment of dynamics around, and protection against, cluster related events.

 

Results:

Despite specificity limitations, we demonstrate that anti-M IgG levels were heterogeneous, reflecting the diversity of circulating emm-types, with highest signals to M4, M89 and M75. Anti-M IgG were significantly lower at birth in all cluster-representative M peptides in newborns than mothers (p<0.0001 for all comparisons), unlike for conserved protein-antigens where IgG levels were comparable. Homologous anti-M IgG responses were significantly higher than unrelated and cluster-homologous responses following culture-confirmed carriage and disease events. Higher cluster-related IgG was associated with reduced odds of events (OR 0.7, 95% CI 0.55–0.98, p=0.003), with low correlation coefficients (0.18-0.26) observed between anti-M and conserved antigen IgG levels.  

 

Discussion:

Anti-M antibodies have low transfer across the placenta and induction of type specific immunity across the life course is heterogenous. Clinical trials with both multivalent M-protein and conserved-antigen vaccines are urgently required in high-burden settings to inform future roll out strategies. 

 

  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)
  3. Smeesters, P. R. et al. Global Streptococcus pyogenes strain diversity, disease associations, and implications for vaccine development: a systematic review. Lancet Microbe 5, e181–e193 (2024).