Novel tuberculosis vaccines based on TB10.4 and Ag85B: State-of-art and advocacy for good practices

Tuberculosis (TB) has plagued humanity in numerous devastating forms for centuries and remains a significant health challenge. Mycobacterium tuberculosis (Mtb), the bacterium responsible for TB, was the leading cause of death among infectious agents until the COVID-19 pandemic emerged. Immunization with the bacillus Calmette-Guérin (BCG) vaccine is one of the primary strategies to mitigate the risk of TB. Despite its widespread use, the current BCG vaccine has limited efficacy, particularly in adults. This review focuses on the rational design of vaccine candidates targeting the antigens TB10.4 and Ag85B. The review discusses the roles of TB10.4 and Ag85B in the virulence of Mtb and notes challenges in their production. Additionally, various protein conjugation strategies to enhance immunogenicity, including linking these antigens to glycans and adjuvants, are considered, as well as the most appropriate analytical methods for characterizing recombinant antigenic proteins and their conjugates. Finally, the associated challenges in developing a vaccine encompassing specific glycans and protein components were highlighted. We claim that using standardized procedures and detailed reporting in protein production and chemical modification can improve the reproducibility and rationalization of biological results. By adhering to these guidelines, the goal of developing an effective vaccine against TB will be best achieved.