Preclinical work showed cyclic‑di‑GMP (c‑di‑GMP) potentiates TLR4‑based vaccine responses against Mycobacterium tuberculosis, improving immunogenicity in animal models. The study demonstrated enhanced antigen presentation and protective immune signatures when c‑di‑GMP was co‑administered, suggesting the molecule could serve as a novel adjuvant for next‑generation TB vaccines. Given the global burden of TB and limits of current BCG protection in adults, an effective adjuvant that boosts TLR4‑driven immunity could be valuable. The authors recommend advancing the adjuvant into formulation and safety studies to evaluate translational potential.