A controlled human infection model of Streptococcus pyogenes pharyngitis (CHIVAS-M75): an observational, dose-finding
Joshua Osowicki1, Kristy I Azzopardi2, Loraine Fabri3
1Tropical Diseases Research Group, Murdoch Children's Research Institute, Melbourne, VIC, Australia; Department of Paediatrics, University of Melbourne, Melbourne, VIC, Australia; Infectious Diseases Unit, Department of General Medicine, Royal Children's Hospital Melbourne, Melbourne, VIC, Australia.
The Lancet. Microbe
|May 11, 2022
Summary
A new human infection model for Streptococcus pyogenes pharyngitis was established. This model shows early safety and can accelerate vaccine development against S. pyogenes infections.
Area of Science:
- Infectious Diseases
- Vaccinology
- Clinical Microbiology
Background:
- Streptococcus pyogenes is a major cause of morbidity and mortality.
- Development of effective vaccines against S. pyogenes is a public health priority.
- Clinically relevant human experimental infection models are needed for vaccine evaluation.
Purpose of the Study:
- To establish a human experimental infection model for Streptococcus pyogenes (S. pyogenes) pharyngitis.
- To identify a safe and effective dose of emm75 S. pyogenes for inducing pharyngitis in volunteers.
- To support the development of novel vaccines and interventions against S. pyogenes.
Main Methods:
- An observational, dose-finding study (CHIVAS-M75) was conducted with healthy volunteers.
- Volunteers were challenged with varying doses of emm75 S. pyogenes via pharyngeal swab.
- Participants were monitored for clinical signs of pharyngitis and confirmed by rapid molecular tests and bacterial culture.
Main Results:
- Pharyngitis was diagnosed in 85% of participants at the initial dose (1-3 × 10^5 CFU/mL).
- Dose de-escalation was performed, with one case of pharyngitis at the lower dose (1-3 × 10^4 CFU/mL).
- Infection was characterized by pharyngeal colonization, elevated inflammatory markers, and modest serological responses. No severe adverse events were reported.
Conclusions:
- A reliable human experimental infection model for S. pyogenes pharyngitis has been established.
- The model demonstrates reassuring early safety findings.
- This model will accelerate the development of vaccines and other interventions for S. pyogenes infections.
