Monash Translational Medicine’s Post

New preprint alert ⏰ My team and I are pleased to share our most recent story about how bacterial pathogen (Streptococcus pyogenes, Strep A) exposure induces antibody responses against glycan and protein antigens. As T cells can’t “see” sugar molecules via their T cell receptor, the text books say that antibody responses to sugars occur without T cell help. T cell help is critical for germinal centres (GC), a specialised lymphoid structure where the antibody sequence on B cells undergo mutations with the aim of increasing binding strength. We asked - is this dogma correct when sugar-specific B cells could engulf whole bacteria? (As they contain proteins for T cells to recognise). We focussed on #StrepA, where the sugar (GAC) is a leading glycoconjugate #vaccine candidate. By studying human blood, spleen and tonsils, including samples from a Strep A human challenge model, we show that sugar B cell responses shift from IgM towards IgG and IgA memory with age and antigen exposure. We found that Strep A infection induced sugar B cells to enter the Germinal centre where they became highly mutated. How were they doing this? By comparing to protein responses (SpyCEP) we found that sugar B cells had a molecular signature consistent with receiving reduced T cell help. We conclude that mucosal pathogen encounters elicit glycan responses that class-switch, evolve and diversify through the GC. ( 📖 👊 take that textbook!) These findings reveal how age and infection history can influence the quality, quantity, and isotype use of sugar-specific B cells. This work has important implications for the design and schedule of glycan-containing vaccines. Congrats to first authors Holly Fryer and Cathy Pitt, and all my co-authors many of whom provided the amazing clinical samples that powered this research. Monash Translational Medicine Murdoch Children's Research Institute (MCRI) Burnet Institute For paper: SSRN  https://lnkd.in/gry_vKNT biorxiv : doi: https://lnkd.in/gvBCtrx6 Key funding from National Health and Medical Research Council (NHMRC), Human Immunome Project Michelson Medical Research Foundation