Immune Responses to Bacillus Calmette-Guérin Vaccination

Bacillus Calmette-Guérin (BCG) remains the only licensed vaccine against tuberculosis, eliciting a complex interplay between innate and adaptive immunity. Upon administration, live attenuated mycobacteria engage pattern recognition receptors on dendritic cells and macrophages, triggering phagocytosis, antigen presentation and the release of pro-inflammatory cytokines. This early innate phase is followed by induction of antigen-specific CD4+ and CD8+ T cells, which secrete interferon-γ and other cytokines crucial for granuloma formation and containment of Mycobacterium tuberculosis. Memory T-cell subsets, including central and effector pools, underpin long-term protection, although their magnitude and durability vary with host age, vaccine strain and route of administration. Beyond tuberculosis, BCG drives epigenetic and metabolic reprogramming of monocytes and natural killer cells, a phenomenon termed trained immunity, which confers heterologous protection against unrelated pathogens. Age-related decline in central memory responses, variable efficacy against adult pulmonary disease and divergent outcomes across global BCG formulations highlight the need for optimised prime-boost strategies, alternative delivery routes and adjuvant formulations to enhance both specific and non-specific protective effects.

Research from Nature Portfolio

Age-related waning of central memory T-cell responses to BCG has been demonstrated in children, revealing that antigen-specific CD4+ effector proliferation remains robust in infancy but diminishes over subsequent years. Parallel increases in γδ T-cell activation and pro-inflammatory cytokine secretion with age suggest a shifting balance between naïve and memory compartments. These findings indicate that a booster dose in school-age children might restore central memory pools and extend protective efficacy against tuberculosis.

Immune Responses to Bacillus Calmette-Guérin Vaccination publication trend

The graph below shows the total number of articles in immune responses to bacillus calmette-guérin vaccination across all publications each year (not limited to Nature Index journals).

Technical terms

Innate immunity: The immediate, non-specific defence mechanism mediated by cells such as macrophages, dendritic cells and natural killer cells.

Adaptive immunity: The antigen-specific response involving T and B lymphocytes, characterised by memory formation and enhanced secondary responses.

Trained immunity: The long-term functional reprogramming of innate cells through epigenetic and metabolic changes, leading to heightened responsiveness upon subsequent challenges.

Central memory T cells: A subset of memory T lymphocytes residing in lymphoid organs that proliferate and differentiate into effector cells upon antigen re-encounter.

Heterologous protection: Vaccine-induced resistance not only to the target pathogen but also to unrelated infectious agents.

References

1. Blood transcriptional correlates of BCG-induced protection against tuberculosis in rhesus macaques. Cell Reports Medicine (2023).
2. Newborn bacille Calmette-Guérin vaccination induces robust infant interferon-γ-expressing natural killer cell responses to mycobacteria. International Journal of Infectious Diseases (2023).
3. Age-related waning of immune responses to BCG in healthy children supports the need for a booster dose of BCG in TB endemic countries. Scientific Reports (2018).
4. BCG as a Case Study for Precision Vaccine Development: Lessons From Vaccine Heterogeneity, Trained Immunity, and Immune Ontogeny. Frontiers in Microbiology (2020).
5. A century of BCG: Impact on tuberculosis control and beyond. Immunological Reviews (2021).