A new study by Maziar Divangahi and his research team describes how Bacille Calmette-Guérin (BCG) vaccination provides additional protection against unrelated pathogens, including influenza A viral infection. Several studies have shown that the BCG vaccine, originally developed to protect against tuberculosis (TB), also significantly reduces childhood mortality from other infectious diseases. This phenomenon is often attributed to the concept of “trained immunity”, which suggests that the BCG vaccine can boost the immune system’s response to various pathogens, not just the TB bacterium.
However, the exact mechanisms by which BCG vaccination provides additional protection against unrelated pathogens are not fully understood. Understanding these mechanisms is a topic of considerable interest, as it could have significant implications for vaccine development and infectious disease control. This study specifically investigated the cellular and molecular mechanisms in BCG-mediated cross-protection against influenza A viral infection. The study highlights that this cross-protection involves interactions between memory T cells (a type of adaptive immune cell) and alveolar macrophages (key innate immune cells in the lungs). Memory T cells are created following an immune response and provide a faster response upon re-exposure to the same pathogen. Alveolar macrophages are resident immune cells in the lungs that play a critical role in responding to respiratory pathogens.
This study demonstrates that BCG vaccination can enhance the interaction between different types of immune cells (adaptive and innate) in the lungs, contributing to improved defense against infections. This interaction is not typically associated with traditional vaccine functions, which usually target specific pathogens. The study provides evidence that this interplay between different types of immune cells can result in cross-protection against infections unrelated to the original target of the vaccine, in this case, an unrelated viral infection like Influenza A virus. The BCG vaccine enriches effector memory T cells and these cells seem to ‘train’ pulmonary innate cells (alveolar macrophages) to more effectively combat the influenza infection by limiting viral replication. Essentially, the immune interactions “train” lung cells to rapidly fight off infection.
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How does the BCG vaccine against TB provide protection against lung viral infections? An RI-MUHC team reveals a new mechanism by which the 100-year-old vaccine provides cross-protection against the influenza A virus. RI-MUHC News. January 19, 2024
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BCG immunization induces CX3CR1hi effector memory T cells to provide cross-protection via IFN-γ-mediated trained immunity. Tran KA, Pernet E, Sadeghi M, Downey J, Chronopoulos J, Lapshina E, Tsai O, Kaufmann E, Ding J, Divangahi M. Nat Immunol. 2024 Jan 15. doi: 10.1038/s41590-023-01739-z. Epub ahead of print. PMID: 38225437