Trends in Immunology
ReviewBCG vaccination induces cross-protective immunity against pathogenic microorganisms
Section snippets
Global relevance of BCG
BCG is a live attenuated vaccine that has been used for over 100 years to prevent infections with M. tb, the causative agent of TB [1]. It is estimated that a quarter of the population worldwide is infected with M. tb [2], resulting in about 1.6 million fatalities each year. This number can be considered one of the highest causes of death from a bacterial disease. Therefore, the control of this epidemic continues to be a global public health problem [3]. According to the 2019 international
Molecular and cellular mechanisms underlying BCG-induced immune responses
BGC is a potent stimulator of the mammalian innate immune response [18], known to engage pattern recognition receptors (PRRs), such as Toll-like receptor (TLR)-2 and TLR-4, which are located on the cell membrane surface [19], and nucleotide-binding oligomerization domain (NOD) receptors situated on the cytosol of innate immune cells such as macrophages, dendritic cells (DCs), and lymphocytes [20]. BCG immunization in mice and humans has also been reported to enhance macrophage trained innate
Trained immunity: heterologous protection by BCG vaccination
Trained immunity is a concept used for the first time in 2011 to indicate the training of innate immune cells upon exposure to certain pathogens or molecules in a sort of innate memory profile [35]. This training allows innate immune cells to respond robustly and rapidly upon challenge with molecules different from the original stimuli [35]. Metabolic and epigenetic changes seem to be responsible for establishing trained immunity in various cell types, as evidenced from particular DNA
BCG-induced cross-protection against bacterial and viral infections
Vaccination with BCG has been described to promote cross-protection against other bacterial and viral infections, resulting in decreased disease outcomes (induced by these pathogens) in humans and mice. In this section, we will specifically discuss the cross-protection that has been documented against non-tuberculosis mycobacteria, other bacteria, fungi, and viruses which has been linked to the trained immunity profile described above.
Putative advantages of BCG-induced cross-immunity for vaccine development
The capacity of BCG vaccination to induce a trained immunity profile against several pathogens, and consequently, cross-reactivity antibodies and stimulation of several T cell subsets in host defense, might potentially help develop new vaccine approaches [92]. Specifically, BCG vaccination induces heterologous immunity, which upon infection with different pathogens, induces the production of IFN-γ and TNF, as described earlier [95]. This nonspecific response against several pathogens has
Concluding remarks
Despite the many years of use of BCG in humans and its positive effects in preventing TB infection, there is a lack of knowledge on how this vaccine can protect against other unrelated infections. In this sense, understanding the mechanisms of induced trained immunity from this vaccine strain is essential for reducing the rates of death and hospitalization due to different infectious agents, that is currently of evident interest when considering the SARS-CoV-2 pandemic (see Outstanding questions
Acknowledgments
This work was supported by FONDECYT grants N° 1190830, FONDECYT Postdoctoral grants N° 3190590, CONICYT scholarship 21190183, 21210662, 21210336, the Millennium Institute on Immunology and Immunotherapy (P09/016-F; ICN09_016), the Innovation Fund for Competitiveness FIC-R 2017 (BIP Code: 30488811-0), Regular grants COPEC-UC2019. R.1169, COPEC-UC2020. E.1. and the Biomedical Research Consortium Chile (13CTI-21526/P4).
Author contributions
Conceptualization, J.A.S, A.M.K., S.M.B.; Writing – original draft, J.A.S., N.M.S.G., C.A.P., M.A.R.; Review and editing, J.A.S., N.M.S.G., C.A.P., C.A.R, A.M.K, S.M.B.
Declaration of interests
The authors declare no conflict of interest.
Glossary
- 5'-methyl-thioadenosine
- a histone methyltransferase inhibitor.
- Arabinomannan
- a polysaccharide of the mycobacterial capsule; important for the classification of different serotypes of the organism, and for vaccine development.
- Buruli ulcer
- disease caused by M. ulcerans that affects the skin and sometimes the bones.
- DC1 phenotype
- a less abundant population of DCs found in peripheral blood. They are noted for their ability to cross-present, effectively prime CD8+ T cells against extracellular antigens
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Mucosal recombinant BCG vaccine induces lung-resident memory macrophages and enhances trained immunity via mTORC2/HK1-mediated metabolic rewiring
2024, Journal of Biological ChemistryTrained immunity: Target for prophylaxis and therapy
2023, Cell Host and MicrobeTrained immunity and epigenetic memory in long-term self-renewing hematopoietic cells
2023, Experimental HematologyImplications of the non-specific effect induced by Bacillus Calmette-Guerin (BCG) vaccine on vaccine recommendations
2023, Jornal de PediatriaCitation Excerpt :In countries where BCG is not part of the vaccination schedule, nontuberculous mycobacterial respiratory infections are more frequent, particularly in patients with cystic fibrosis and bronchiectasis of other etiologies.1 Protection against C. albicans and other bacteria such as S. pneumoniae and H. influenzae possibly occur through cross-protection.35 Epidemiological studies in several countries have shown that the BCG vaccine was associated with a reduction in childhood morbidity and mortality beyond what would be expected for protection against TB.
Trained immunity-related vaccines: innate immune memory and heterologous protection against infections
2022, Trends in Molecular MedicineCitation Excerpt :Additionally, activation of trained immunity conferred wide-spectrum protection against a broad panel of clinically relevant bacterial infections [43]. Similar effects were also observed to be induced by vaccines, with most of our knowledge regarding trained immunity in humans deriving from studies with Bacille Calmette–Guérin (BCG) vaccine, a live attenuated strain derived from an isolate of Mycobacterium bovis, developed a century ago against TB [44,45]. Trained immunity properties induced by vaccines were first identified almost a decade ago in a mouse model of lethal Candida albicans infection in which BCG-treated mice exhibited significantly better survival rates and decreased fungal burden after vaccination compared with controls [8].