Journal Article

Immunological mechanistic action of intravenous BCG-mediated protection against tuberculosis

Lee, Ju Mi, Park, Jiyun, Shin, Sung Jae, Hong, Jung Joo, Choi, Sangwon

2026

Overview

The Bacillus Calmette-Guérin (BCG) vaccine, the only licensed vaccine against tuberculosis (TB), has played a crucial role in mitigating severe manifestations of the disease, particularly in children. However, its effectiveness against pulmonary TB in adults remains variable, largely due to its limited ability to elicit a sustained antigen-specific T H 1 immune response and to generate long-lived tissue-resident memory T cells (T RM ) within the lungs. Consequently, innovative strategies that address these immunological shortcomings are needed to enhance BCG immunogenicity and efficacy against pulmonary TB. Recent studies on intravenous (IV)-BCG have emerged as a promising alternative, achieving near-sterilizing immunity in preclinical models such as nonhuman primates by strengthening pulmonary defenses against Mycobacterium tuberculosis (Mtb). This review examines how IV-BCG enhances BCG efficacy through a synergistic network of immunological factors, including trained immunity, effector T H 1 cells, lung T RM , inducible bronchus-associated lymphoid tissue (iBALT), and antibody responses. Systemic delivery of IV-BCG induces durable trained immunity, primes robust T H 1 and T RM responses in the lungs, may foster iBALT formation for localized protection, and enhances antibody production to reinforce humoral defenses. Drawing on data from preclinical studies, this review highlights how these components interconnect to sustain long-lasting pulmonary protection and offers insights into optimizing BCG-based TB vaccines.

• Publisher: Springer International Publishing,Springer Nature B.V,Springer
• Subject: Animal models / Animals / Antibodies / Antibody responses / Antigens / Bacillus Calmette-Guerin vaccine / BCG / BCG Vaccine - administration & dosage / BCG Vaccine - immunology / BCG Vaccine - therapeutic use / Biochemistry / Biomedical and Life Sciences / Biomedicine / Bone marrow / Bronchus / Cell Biology / Cells / Cytokines / Effectiveness / Effector cells / Epigenetics / Granulomas / Humans / iBALT / Immune response / Immune system / Immunity / Immunity (Disease) / Immunogenicity / Immunologic Memory / Immunological memory / Immunology / Infections / Intravenous administration / Intravenous BCG / Life Sciences / Lung - immunology / Lung - microbiology / Lungs / Lymphatic system / Lymphocytes / Lymphocytes T / Lymphoid tissue / Memory cells / Meningitis / Mycobacterium tuberculosis - immunology / Review / Spleen / Th1 Cells - immunology / Trained Immunity / TRM / Tuberculosis / Tuberculosis - immunology / Tuberculosis - prevention & control / Tuberculosis, Pulmonary - immunology / Tuberculosis, Pulmonary - prevention & control / Vaccines