Efficacy of Mycobacterium vaccae and vitamin D combination therapy in initial smear-negative pulmonary tuberculosis: a prospective study

Purpose To evaluate the efficacy of adjunctive Mycobacterium vaccae ( M. vaccae ) and vitamin D in patients with initial smear-negative pulmonary tuberculosis (PTB) and to explore their effects on immune responses. Methods In this prospective cohort study, 391 patients with initial smear-negative pulmonary tuberculosis were consecutively enrolled and followed for 4 months. Patients were assigned to one of three treatment groups: standard anti-tuberculosis therapy (control), standard therapy plus M. vaccae vaccination, and standard therapy combined with M. vaccae and vitamin D. Cytokine levels [interferon-γ (IFN-γ), interleukin-4 (IL-4), IL-17, IL-10], T cell subset ratios [Th1/Th2, Th17/regulatory T cells (Treg)], and clinical outcomes were prospectively assessed. Results The combined therapy group showed significant increases in IFN-γ and Th1/Th2 ratio, and decreases in IL-4, IL-17, IL-10, and an increase in the Th17/Treg ratio, indicating a shift toward Th1-dominant immunity. Clinically, lesion absorption (54.33%) and cavity closure (71.13%) rates were highest in the combined group, with a total effective rate of 89.76%, surpassing the control (76.12%) and M. vaccae (79.23%) groups ( p < 0.05). Conclusion Adjunctive therapy with M. vaccae and vitamin D enhances immune function and improves clinical outcomes in initial smear-negative PTB, suggesting a synergistic immunotherapeutic effect.