Tuberculosis vaccines: time to think about the next generation

Area of Science:

• Vaccinology
• Infectious Diseases
• Microbiology

Background:

• Significant research over 20 years has yielded a robust pipeline of tuberculosis (TB) vaccines.
• The current Bacillus Calmette-Guérin (BCG) vaccine offers limited protection against active TB in adults.
• Existing TB vaccine candidates focus on preventing active disease, not eliminating Mycobacterium tuberculosis (Mtb) infection.

Purpose of the Study:

• To review the current landscape of TB vaccine development.
• To highlight the limitations of existing vaccine strategies.
• To advocate for novel approaches targeting Mtb infection and preventing TB reactivation.

Main Methods:

• Review of the current TB vaccine research and development pipeline.
• Analysis of the proposed mechanisms of action for novel TB vaccine candidates.
• Assessment of the clinical trial status and limitations of current TB vaccines.

Main Results:

• Numerous TB vaccine candidates are in advanced clinical development, aiming for pre- or post-exposure administration.
• Most current vaccines aim to quantitatively improve upon BCG's efficacy in preventing active TB.
• No current vaccine strategies are designed to prevent or eliminate Mtb infection, a crucial step for preventing TB reactivation.

Conclusions:

• The current TB vaccine pipeline shows promise for preventing active disease but falls short of eliminating Mtb infection.
• Qualitatively superior vaccines capable of preventing or eliminating Mtb infection are needed.
• Radically new strategies are required to develop vaccines that can prevent Mtb infection and lifelong TB risk.