Oral Presentation Lancefield International Symposium for Streptococci and Streptococcal Diseases 2025

Experimental human infection with Streptococcus pyogenes alters the magnitude and phenotype of vaccine antigen-specific memory B cells (116679)

Holly A Fryer 1 , Catherine Pitt 1 , Hannah R Frost 2 , Nitika Kandhari 1 3 , Alana L Whitcombe 4 5 , Pailene S Lim 6 7 , Stephen W Scally 6 7 , Nikki J Moreland 4 5 , David M Tarlinton 8 , Joshua Osowicki 2 9 10 , Andrew C Steer 2 9 10 , Danika L Hill 1 2
  1. Precision Vaccinology Laboratory, Monash University, Melbourne, Victoria, Australia
  2. Tropical Diseases Research Group, Murdoch Children's Research Institute, Melbourne, Victoria, Australia
  3. Monash Genomics and Bioinformatics Platform, Monash University, Melbourne, Victoria, Australia
  4. Maurice Wilkins Centre for Molecular Biodiscovery, University of Auckland, Auckland, New Zealand
  5. School of Medical Sciences, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand
  6. Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia
  7. Department of Medical Biology, University of Melbourne, Melbourne, Victoria, Australia
  8. Immune Memory Laboratory, Monash University, Melbourne, Victoria, Australia
  9. Department of Paediatrics, University of Melbourne, Melbourne, Victoria, Australia
  10. Department of Infectious Diseases, Royal Children's Hospital Melbourne, Melbourne, Victoria, Australia

Background

Encounters with the ubiquitous human commensal and common pathogen Streptococcus pyogenes occur repeatedly over the human lifespan. There are still critical areas of uncertainty regarding how the human immune system recognises, responds to, and remembers S. pyogenes, hindering modern vaccine development. Here, we investigated B cell responses to leading S. pyogenes candidate vaccine antigens.

Methods

The recently developed human challenge model of emm75 S. pyogenes pharyngitis in healthy adults (CHIVAS-M75) presents a unique opportunity to characterise pre-existing immunity and the nature of recalled immune memory upon repeat exposure. Using peripheral blood mononuclear cells collected before and after challenge, we used flow cytometry and single-cell sequencing approaches to compare B cell responses to S. pyogenes vaccine antigens (including SpyCEP, SpyAD, SCPA, and SLO) in CHIVAS-M75 challenge trial participants, comparing those who did and did not develop pharyngitis.

Results

We characterised how infection changes the magnitude, gene expression, phenotype, and B cell receptor repertoires of vaccine antigen-specific memory B cells. Overall, pre-existing memory B cell responses to were common in these healthy adults, and responses were modified by the experimental infection. The proportion of antigen-specific isotype class-switched B cells increased post-challenge, suggesting a maturation of cellular memory upon pathogen encounter. Increases in antigen-specific B cells correlated with antigen-specific serum IgG at 3 months post-challenge.

Conclusion

Our work provides foundational insights into how a single infection shapes immunity and its relationship to symptomatic infection, and suggests that pre-existing B cell memory may influence S. pyogenes vaccine immunogenicity in clinical trials in adults.