Oral Presentation 16th Lorne Infection and Immunity 2026

Antibody responses against bacterial glycans affinity mature and diversify in germinal centers (131897)

Holly A Fryer 1 , Catherine Pitt 1 , Hannah R Frost 2 , Nitika Kandhari 1 3 , Sean Byars 3 , Pailene S Lim 4 5 , Rhiannon L Fettes 1 , Reece W Lovett 1 , Trang T Nguyen 6 , Kaneka Chheng 2 , Natalie Caltabiano 2 , Alana L Whitcombe 7 8 , Julianne Hamelink 9 10 11 , Dean Andrew 9 , Gareth Lloyd 12 , Brian Wilson-Boyd 12 , Nicola Slee 12 , Jodie Ballantine 12 , Sarju Vasani 13 , Kathryn Girling 13 , Liam Gubbels 2 , Eric Levi 2 , Karen Davies 14 , Stuart G Tangye 15 , Jonathan Noonan 16 , Nikki J Moreland 7 8 , Isaak Quast 17 , Marcus Robinson 17 , Stephen W Scally 4 5 , Melanie Neeland 2 18 , Shivanthan Shanthikumar 2 18 19 , Joshua Osowicki 18 20 21 , David M Tarlinton 17 , Andrew C Steer 18 20 21 , Michelle J Boyle 11 21 22 , Danika L Hill 1 20
  1. Precision Vaccinology Laboratory, Monash University, Melbourne, Victoria, Australia
  2. Infection, Immunity and Global Health Theme, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
  3. Monash Genomics and Bioinformatics Platform, Monash University, Melbourne, Victoria, Australia
  4. Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
  5. Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia
  6. Immunology, Monash University, Melbourne, Victoria, Australia
  7. Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand
  8. School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
  9. QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
  10. University of Queensland, Brisbane, Queensland, Australia
  11. Burnet Institute, Melbourne, Victoria, Australia
  12. Queensland Children's Hospital, Brisbane, Queensland, Australia
  13. Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia
  14. Otolaryngology, Royal Children’s Hospital, Melbourne, Victoria, Australia
  15. Garvan Institute of Medical Research, Sydney, NSW, Australia
  16. Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia
  17. Immune Memory Laboratory, Monash University, Melbourne, Victoria, Australia
  18. Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
  19. Respiratory and Sleep Medicine, Royal Children’s Hospital, Melbourne, Victoria, Australia
  20. Tropical Diseases Research Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
  21. Department of Infectious Diseases, Royal Children's Hospital Melbourne, Melbourne, Victoria, Australia
  22. Department of Immunology, Monash University, Melbourne, Victoria, Australia

Glycoconjugate vaccines have been effective against many major human pathogens, however the generation of glycan-specific antibodies remains poorly understood. Purified carbohydrates are believed to elicit T-independent responses, but in humans some anti-glycan antibodies show signs of germinal center (GC) experience. We studied human B cell responses to Streptococcus pyogenes, a deadly pathogen without a vaccine, where glycoconjugate vaccine candidates are advanced in development. By simultaneously assessing S. pyogenes protein and glycan antigen-specific B cell responses across blood, spleen, tonsils, and in human challenge participants, we reveal that glycan-binding B cells shift from IgM towards IgG and IgA memory with age and antigen exposure. Both natural colonization and controlled human infection with S. pyogenes increased class-switched B cells, with evidence of within-clone switching. Glycan-specific B cells readily engaged in GC responses and underwent robust somatic hypermutation, but had reduced expression of T cell help-associated molecules, correlating with lower antibody-secreting cell output compared to a protein-specific response occurring in parallel. We conclude that mucosal pathogen encounters elicit glycan-specific B cell responses that class-switch, evolve and diversify through the GC. These findings reveal how age and infection history can influence the quality, quantity, and isotype usage of glycan-specific B cells, with implications for the design and schedule of glycan-containing vaccines.