Efficacy and safety of bacterial immunostimulants in immunodeficient individuals: A systematic review and meta‐analysis

BACKGROUND: Bacterial immunostimulants, such as lysates and trained-immunity vaccines, reduce recurrent respiratory infections and modulate immunity in immunodeficient patients. However, heterogeneity of preparations and limited safety data call for standardized evaluation. OBJECTIVE: To assess the efficacy, immune effects, and clinical outcomes of bacterial immunostimulants in immunodeficient individuals. METHODS: This systematic review followed PRISMA 2020 guidelines. Searches were conducted in PubMed, Web of Science, EMBASE, and Cochrane Library, as well as in regional databases (AJOL, IMEMR, LILACS), and national databases including Chinese and Russian scientific resources. We included full-text clinical studies on bacterial lysates in immunodeficient patients. Fourteen original studies were identified. Meta-analysis was performed when ≥3 studies reported comparable quantitative outcomes. RESULTS: Studies assessed bacterial immunostimulants in primary (IgA deficiency, IgG subclass deficiency, CVID, hypogammaglobulinemia) and secondary (HIV infection, nephrotic syndrome, hemodialysis patients) immunodeficiencies. OM-85 (bacterial lysate) significantly reduced acute respiratory tract infections (ARTIs) in patients with mild immunodeficiency compared to baseline (MD -3.52, 95% CI: -5.06 to -1.98) and controls (MD -1.75, 95% CI: -2.71 to -0.78), despite high heterogeneity. Immunological outcomes were inconsistent: IgA levels showed a slight, non-significant increase, while the rise in IgG concentrations was heterogeneous and not robust to sensitivity analyses. No evidence of autoimmune activation was documented. CONCLUSIONS: Bacterial immunostimulants, particularly OM-85, show promise as adjuncts in the management of immunodeficiencies by reducing ARTIs and antibiotic use, and enhancing immune responses. They are well-tolerated, with no evidence of pathological immune activation. However, study heterogeneity and methodological differences limit comparability.