Jelle Klein
Medical Director, SGS
Controlled human infection models can accelerate vaccine efficacy testing and treatment validation for malaria, dengue, tuberculosis and other tropical diseases.
Tropical diseases, including malaria, dengue and tuberculosis impose a significant global health challenge, with millions of cases reported worldwide. Existing preventive treatments often fall short, necessitating the development of new vaccines and antimicrobial therapies. However, progress is slow, and demand for solutions is high.
Accelerating treatment development with CHIMs
Controlled human infection models (CHIMs) offer a strategy to accelerate treatment development. By inoculating healthy participants with a controlled pathogen, it is possible to test for treatment efficacy or identify vaccine correlates of protection. This approach ensures the precise timing of inoculation, facilitating advanced biomarker assays. It helps differentiate between promising and weak treatment candidates quickly.
Optimising malaria infection models
In a recent example, a GMP-manufactured Plasmodium Falciparum NF54 strain is accessible for clinical trials. Through a titration trial conducted collaboratively with the strain’s owner, SGS experts determined the optimal infectious dose for this strain. This ensured ample parasite supply, enabling a meaningful comparison between active treatment and placebo while maintaining mild to moderate symptoms for participants.
CHIMs are a powerful tool to establish early proof-of-concept of vaccine efficacy in humans.
Versatility of CHIMs in tropical disease development
CHIMs are a powerful tool to establish early proof-of-concept of vaccine efficacy in humans. These models have already assisted with the selection of vaccine candidates for diseases including cholera, E. coli, malaria, shigella, streptococcus pneumoniae, tuberculosis, typhoid and H. pylori.
CHIMs are particularly valuable when the pathogen process is sufficiently understood, the agent can be GMP manufactured, and rescue treatments are available. For instance, tuberculosis, with its known pathogen process and established treatments like isoniazid, rifampin, pyrazinamide and ethambutol, could be effectively utilised in this model. Dengue CHIM trials, featuring DENV type I, have also been successfully conducted.
Advancing treatment solutions for pharmaceutical companies
Incorporating CHIMs into tropical disease drug/vaccine development provides essential data for precise field trial design. These models enable controlled testing, validating treatment efficacy or rapid termination if ineffectiveness is evident. With careful trial design, CHIMs become invaluable tools for advancing tropical disease treatments, benefiting pharmaceutical companies aiming to address critical infectious disease challenges.