Challenges in developing new tuberculosis vaccines

Tuberculosis (TB) is a preventable and curable disease caused by the bacillus Mycobacterium tuberculosis. In 2022, according to the World Health Organisation (WHO), TB was the second leading cause of death worldwide caused by a single infectious agent, after coronavirus disease (COVID-19). Brazil is ranked among the 30 countries with the highest TB burden. Currently, the neonatal Bacillus Calmette-Guérin (BCG) is the only vaccine against TB and offers significant efficacy against disseminated and meningeal disease in children. However, BCG has a limited efficacy in preventing adult-type cavitary TB, reinforcing the need for a new effective vaccine against pulmonary TB. There are currently over 22 TB vaccines under evaluation in clinical trials worldwide. Despite significant advancements, several challenges persist in developing and producing an effective TB vaccine. These include understanding the immune mechanisms that confer protection against M. tuberculosis, identifying immune correlates of protection, defining immune responses in BCG-vaccinated individuals, establishing efficacy endpoints for TB vaccine trials, and ensuring vaccine safety and effectiveness in individuals with human immunodeficiency virus (HIV), among other obstacles. Therefore, this study aims to explore the key obstacles in developing new TB vaccines and potential strategies to overcome them.