Researchers reported preclinical evidence that c‑di‑GMP enhances TLR4‑targeted vaccine efficacy against Mycobacterium tuberculosis by amplifying innate sensing and adaptive responses. The study, led by Kwon et al., demonstrated improved protection in animal models when the second messenger c‑di‑GMP was formulated with a TLR4 agonist. C‑di‑GMP is a bacterial cyclic dinucleotide that activates cytosolic sensors and can act as an adjuvant to boost cellular immunity; the paper positions it as a candidate to augment TB vaccine candidates that require strong Th1 responses. For infectious disease vaccinology, the result identifies a modular adjuvant strategy that could be tested in clinical development to improve durable protection against TB.