In 2025, the WHO published guidance on CHIM use during public-health emergencies, focusing on seven core criteria: (1) strong scientific justification; (2) rigorous assessment that expected benefits outweigh risks; (3) coordination with wider emergency research plus expert/public engagement; (4) careful site selection ensuring highest scientific/clinical/ethical standards; (5) risk-limiting participant selection; (6) appropriately qualified independent review; and (7) robust, ongoing informed consent.
Milestone
4.2.c
Standard Operating Procedures
In progress
High priority
Establish SOPs for CHIM use in coronavirus vaccine research, including risk mitigation strategies, serological screening, inoculation method, quarantine duration, standardization of sampling, and data and sample sharing, that reflect the changing landscape of disease and therapeutics.
Progress Highlights
The Imperial College of London has completed multiple CoV CHIM studies. Best practices can be gleaned from their work, and from workshops on the ethics and regulation of CHIM studies:
Ethical and regulatory considerations
CHIM studies require:
Rigorous ethical approval
- Jamrozik 2024: Ethical approval for controlled human infectious model clinical trial protocols—a workshop report
Informed consent with transparent risk-benefit communication
Risk minimization (selecting low-risk participants)
- Killingley 2022: Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults
Community engagement to enhance public trust and study design
Study design and methodology
Standardized protocols ensure data comparability.
Virus selection and dose optimization require well-characterized strains and strict biosafety measures, including quarantine, to prevent unintended pathogen spread.
- McKendry 2024: Human challenge studies with coronaviruses old and new
- Zhou 2023: Viral emissions into the air and environment after SARS-CoV-2 human challenge: a phase 1, open label, first-in-human study
Safety and monitoring
Continuous medical supervision enables early intervention for adverse events.
- Killingley 2022: Safety, tolerability and viral kinetics during SARS-CoV-2 human challenge in young adults
Immune response assessments help identify disease progression markers.
- Rosenheim 2024: SARS-CoV-2 human challenge reveals biomarkers that discriminate early and late phases of respiratory viral infections
- Wagstaffe 2024: Mucosal and systemic immune correlates of viral control after SARS-CoV-2 infection challenge in seronegative adults
Detailed profiling of local and systemic responses enhances understanding of infection dynamics.
Data integrity and scientific contributions
Ensuring reproducibility and robust data collection improves reliability.
Investigating genetic and immunological factors (e.g. HLA associations) helps assess disease susceptibility.
Studying viral shedding informs public health strategies.