Eldy Akhirul Akbar, Tukiran Tukiran, I. Gusti Made Sanjaya, Rudiana Agustini, Muhammad Nurrohman Sidiq
Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a major global health burden despite widespread Bacillus Calmette–Guérin vaccination, which provides inconsistent protection against adult pulmonary TB. This systematic review, conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, synthesizes recent advances in TB vaccine development, encompassing conventional live-attenuated and protein subunit vaccines as well as computationally designed multi-epitope vaccines (MEVs). A comprehensive literature search of PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar for studies published between January 2020 and December 2024 identified 847 records, of which 63 met inclusion criteria for qualitative synthesis. Clinical-stage development remains dominated by conventional platforms, with M72/AS01E demonstrating 54% efficacy in a Phase 2b trial and advancing to Phase 3 evaluation, representing the most prom-ising next-generation candidate to date. In parallel, immunoinformatics and reverse vac-cinology (RV) approaches have enabled rational MEV design, including constructs such as PP13138R and PP19128R, which exhibit strong antigenicity and immunogenicity in silico and in vitro. Novel hypothetical protein antigens, including Rv3899c, Rv1509, Rv0574c, and Rv0790c, have also emerged as potential targets. However, no computationally designed MEV has yet progressed to clinical evaluation, highlighting a significant translational gap between predictive modeling and experimental validation. TB vaccine research is increas-ingly transitioning toward rational, computationally guided strategies, but integration of computational discovery with rigorous preclinical and clinical validation remains essential to accelerate the development of effective next-generation TB vaccines. © Korean Vaccine Society and Korean Society for Zoonoses.
Department of Chemistry, Faculty of Mathematics and Natural Science, Universitas Negeri Surabaya, Surabaya, Indonesia
