Candidate Vaccines against Tuberculosis and the Future of Novel TB Vaccine Research

Abstract

Introduction: Tuberculosis (TB) continues to be a global health challenge and currently only one licensed vaccine is available. For nearly 100 years, the Bacillus Calmette-Guérin (BCG) vaccine has been in use. While it provides protection against disseminated TB in infants, its protection against adult and adolescent pulmonary tuberculosis (PTB) is variable. This literature review will provide an overview of the clinical status of candidate TB vaccines and discuss the challenges and future development trends of novel TB vaccine research, in combination with a general overview of the Tuberculosis (TB) disease and Mycobacterium tuberculosis itself. Methods: Bibliographic searches were carried out on medical journal databases, publishers, and aggregators. The most used databases were PubMed, NCBI and MDPI. Publications in English on these and other databases relating to novel TB vaccines were included in this review. Results: Currently, there are 12 main vaccine candidates in various phases of clinical trials, they include four protein or adjuvant vaccines, three viral-vectored vaccines, three mycobacterial whole cells or extract vaccines, and one each of the recombinant life and the attenuated Mycobacterium tuberculosis vaccine. Currently, the most likely candidate vaccines are the M72 + AS01E and Vaccae vaccines. M72 + AS01E is a recombinant fusion protein vaccine candidate, clinical trials showed that administering two doses of M72/AS01E was successful in reducing the development of active TB disease with 50% efficacy. Studies have also proven the efficacy of Vaccae (which is currently in phase III clinical trials) as an adjunctive therapy, with it being curative in conjunction with current therapy. Conclusion: Given the morbidity and mortality suffered globally by M. tuberculosis, it is time to realize the seriousness of the situation and accelerate our commitment and investment to the eradication of this infectious disease. With the number of vaccine candidates currently in clinical trials having promising results, it is imperative to continue these studies and accelerate towards phase III licensure trials if we are to achieve the milestone of “End TB Strategy” by 2035. Today, we are witnessing immense progress in both preclinical and clinical TB vaccine research despite disappointing results from some of the clinical efficacy trials like that of MVA85A. We can revisit the design of vaccines and learn from them. It is important not only to recognize and give credit to those that have tested well in human trials, such as M72 + AS01E, but to expedite and improve its efficacy through funding of its research.