Innovative clinical trial designs to rationalize TB vaccine development

Area of Science:

• Vaccinology
• Infectious Diseases
• Clinical Trials

Background:

• Developing effective tuberculosis (TB) vaccines faces significant hurdles, including unknown correlates of protection and limitations of preclinical models.
• Large-scale efficacy trials for TB vaccines require substantial sample sizes, even in high-burden populations.

Purpose of the Study:

• To evaluate a leading TB vaccine candidate in a large infant trial.
• To underscore the difficulties in TB vaccine development and explore alternative clinical trial strategies.

Main Methods:

• A Phase 2b efficacy trial involving 3000 South African infants was conducted.
• Novel clinical trial models using biologically relevant outcomes and innovative statistics were developed.

Main Results:

• The TB vaccine candidate did not demonstrate protection beyond that offered by the BCG vaccine alone.
• The trial results emphasize the challenges in predicting human vaccine efficacy from preclinical data.

Conclusions:

• Current TB vaccine development pathways are difficult and require significant refinement.
• Novel clinical trial models offer a more rational approach to selecting TB vaccine candidates for large-scale testing.