Efficacy, immunogenicity, and safety of BCG revaccination against Mycobacterium tuberculosis: A systematic review and meta-analysis

Tuberculosis (TB) remains a leading global cause of death. While primary Bacillus Calmette-Guérin (BCG) vaccination offers protection in children, the role of BCG revaccination in adults remains unclear. This study evaluated the efficacy, immunogenicity, and safety of BCG revaccination against TB. A comprehensive literature search through July 2025, with independent data extraction by two reviewers. RevMan version 5.4 was used for analysis by applying random-effects models with 95% CIs. Six RCTs, involving 2400 participants, showed no significant effect of BCG revaccination on initial (RR 0.99) or sustained (RR 0.80) QFT conversion, showing only modest effectiveness against MTB. Immunogenicity evaluation showed a moderate increase in CD8+ T cell (<i>p</i> = .01) and cytokine-producing CD4+ T cell responses (<i>p</i> = .008). Safety analysis indicated increased adverse events, though a reduced risk of upper respiratory tract infections (RR 0.37) was noted. These results highlight a discrepancy between immune activation and quantifiable protection, suggesting limited BCG revaccination benefit in high-risk groups and the need for vaccines with proven protective immunity.