Controlled human infection models in COVID-19 and tuberculosis: current progress and future challenges

Area of Science:

• Infectious Diseases
• Vaccinology
• Immunology

Background:

• Controlled Human Infection Models (CHIMs) are crucial for studying disease progression and evaluating interventions.
• CHIMs are under development for tuberculosis (TB) and Covid-19, facing optimization challenges.
• Ethical considerations necessitate surrogate models for virulent pathogens like *Mycobacterium tuberculosis*.

Purpose of the Study:

• To review progress and future directions of CHIMs for TB and Covid-19.
• To discuss the application of CHIMs in understanding disease kinetics and immune responses.
• To highlight the utility of CHIMs in assessing novel vaccines and therapeutics.

Main Methods:

• Development of CHIMs using surrogate mycobacteria or genetically modified strains for TB.
• Utilizing intranasal CHIMs with SARS-CoV-2 to study viral kinetics and immune responses.
• Employing various administration routes (aerosol, bronchoscope, intradermal) for CHIMs.

Main Results:

• CHIMs enable detailed study of disease processes and evaluation of prevention/treatment methods.
• SARS-CoV-2 CHIMs are used to assess viral kinetics and immunological responses.
• Surrogate models for TB are being developed due to ethical constraints.

Conclusions:

• CHIMs are vital tools for advancing TB and Covid-19 research, vaccine development, and therapeutic evaluation.
• Ongoing refinement of CHIMs is essential for their effective application.
• The dynamic nature of the Covid-19 pandemic presents unique challenges and opportunities for CHIM development.