Background: The CHIVAS-M75 study established the world’s only modern Streptococcus pyogenes human challenge model as a focal point for infection, immunity, and vaccine research and development. The model’s safety and reliability has recently been highlighted in a trial to determine the protective plasma concentration of penicillin against experimental human pharyngitis (the CHIPS trial). We will expand the S. pyogenes human challenge model’s potential by introducing an M1UK strain, the current dominant variant from the M1 lineage.
Methods: CHIVAS-M1 will establish the dose of S. pyogenes M1UK to safely and reliably cause pharyngitis in ≥60% of participants. Doses of the M1UK challenge strain will be manufactured according to principles of Good Manufacturing Practice. Up to 50 healthy adults at low risk for complicated S. pyogenes disease will be challenged in sequential cohorts, in a dose-finding inpatient study starting at the level confirmed in CHIVAS-M75 – direct pharyngeal application with a swab from a single-dose vial containing 1-5 x 105 CFU in 1 mL liquid media.
Results: Participants will be closely monitored as inpatients for up to 5 days and will receive antibiotic treatment prior to discharge, regardless of pharyngitis diagnosis. A diverse range of throat swab, oral fluid, and blood samples will be collected before, during, and after the admission.
Conclusion: CHIVAS-M1 will establish a second strain in the pharyngitis human challenge model, introducing capacity for homologous and heterologous rechallenge studies, and increasing the generalisability of findings emerging from the model, including in trials to evaluate the efficacy of candidate vaccines.