[Status of Tuberculosis Vaccines Development in Clinical Trials]

Tuberculosis (TB) is the leading cause of death worldwide before the corona virus pandemic, but the only licensed vaccine to date is Bacillus Calmette-Guérin (BCG). This manuscript aims to introduce the current status and trends of clinical research on TB vaccines, one of the most difficult vaccines to develop.

To identify the current status of clinical development, we reviewed the literature on TB vaccine candidates currently in the clinical pipeline and the World Health Organization (WHO) reports on the introduction of new vaccine developments.

As of September 2024, 15 TB vaccines candidates are in the clinical pipeline. Across vaccine platforms, six whole-cell, five recombinant protein, two viral vector-based, and two mRNA vaccines are in clinical development, with the largest number of candidates being whole-cell-based vaccines. As of 2024, two mRNA vaccines are also in Phase 1 clinical trials. WHO predicts that a new TB vaccine will be available within five years. The recombinant protein-based M72/AS01_E vaccine has been mentioned as a potential vaccine, and is currently recruiting subjects for a Phase 3 clinical trial. In addition, recombinant protein-based GemTBvac and whole cell-based MIP, MTBVAC, and VPM1002 are in Phase 3 clinical trials.

While several platform-based TB vaccine candidates are in clinical trials; however, the antigens contained in these candidates are often redundant and limited. To diversify the TB vaccine clinical pipeline, it is necessary to continue research to identify new antigens, the development of preclinical animal models for efficacy evaluation, and the identification of valid endpoints through the analysis of clinical trial results are necessary.