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Review
. 2021 Oct;18(10):611-622.
doi: 10.1038/s41585-021-00481-1. Epub 2021 Jun 15.

100 years of Bacillus Calmette-Guérin immunotherapy: from cattle to COVID-19

Niyati Lobo  1 , Nathan A Brooks  1 , Alexandre R Zlotta  2   3 , Jeffrey D Cirillo  4 , Stephen Boorjian  5 , Peter C Black  6 , Joshua J Meeks  7 , Trinity J Bivalacqua  8 , Paolo Gontero  9 , Gary D Steinberg  10 , David McConkey  11 , Marko Babjuk  12 , J Alfred Witjes  13 , Ashish M Kamat  14
Affiliations
Review

100 years of Bacillus Calmette-Guérin immunotherapy: from cattle to COVID-19

Niyati Lobo et al. Nat Rev Urol. 2021 Oct.

Abstract

Bacillus Calmette-Guérin (BCG) is the most widely used vaccine worldwide and has been used to prevent tuberculosis for a century. BCG also stimulates an anti-tumour immune response, which urologists have harnessed for the treatment of non-muscle-invasive bladder cancer. A growing body of evidence indicates that BCG offers protection against various non-mycobacterial and viral infections. The non-specific effects of BCG occur via the induction of trained immunity and form the basis for the hypothesis that BCG vaccination could be used to protect against the severity of coronavirus disease 2019 (COVID-19). This Perspective article highlights key milestones in the 100-year history of BCG and projects its potential role in the COVID-19 pandemic.

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Conflict of interest statement

S.B. declares that he has acted as a consultant for Ferring, Sanofi, ArTara and FerGene. P.C.B. declares that he is an advisory board member or equivalent for AbbVie, Asieris, AstraZeneca, Astellas, Bayer, Biosyent, BMS, EMD-Serono, Ferring, Fergene, H3-Biomedicine, Janssen, Merck, Roche, Sanofi, Urogen. He has received grant support or honoraria from iProgen, Sanofi, Bayer and GSK. P.C.B also holds a patent with Decipher Biosciences. J.J.M. declares that he acts as a consultant for Merck, AstraZeneca, Ferring, Cold Genesys, Janssen, Nucleix and Foundation Medicine. He has received research funding from AbbVie, Tesaro and Epizyme. D.M. declares that he has received grant support from AstraZeneca, Rainer Pharmaceuticals and honoraria from Janssen, Rainier Pharmaceuticals and H3 biomedicine. T.J.B. declares that he has acted as a consultant for FerGene, Genesis Biotechnology and Photocure. G.D.S declares that he is a member of clinical trial protocol committees for Merck, BMS, Janssen, Cold Genesys, Pfizer, PhotoCure and Fidia. He is or has been a scientific advisor/consultant within the past 5 years for Heat Biologics, Cold Genesys, PhotoCure, Merck, Roche/Genentech, Ciclomed, Taris Biomedical, MDxHealth, Fidia Farmaceuticals, Urogen, Ferring, Aduro, Boston Scientific, Bristol Myers Squibb, AstraZeneca, Pfizer, Janssen, Epivax Oncology, Natera, FKD, Ferring, EnGene Bio, SesenBio, BioCanCell, Nucleix, Ipsen, Combat Medical, Astellas, Fergene, Dendreon, AbbVie and Seattle Genetics. A.M.K. is a consultant or advisory board member for Abbott Molecular, Arquer Diagnostics, ArTara Therapeutics, Asieris Pharmaceuticals, AstraZeneca, BioClin Therapeutics, Bristol Myers Squibb, Cepheid, Cold Genesys, Eisai, Engene, Ferring Pharmaceuticals, FerGene, Imagine Pharma, Janssen, MDxHealth, Medac, Merck, Pfizer, Photocure, ProTara Therapeutics, Roviant Sciences, Seattle Genetics, Sessen Bio, Theralase Technologies, TMC Innovation and US Biotest. A.M.K. has received grants and/or research support from Adolor Corporation, Bristol Myers Squibb, FKD Industries, Heat Biologics, Merck, Photocure, SWOG/NIH, Specialized Programs of Research Excellence (SPORE) and AIBCCR. A.M.K. also holds the patent for Cytokine Predictors of Response to Intravesical Therapy (CyPRIT) joint with UT MD Anderson Cancer Center. The other authors declare no competing interests.

Figures

Fig. 1
Fig. 1. The history of Bacillus Calmette–Guérin (BCG) from discovery to use in COVID-19.
FDA, US Food and Drug Administration; NMIBC, non-muscle-invasive bladder cancer; TB, tuberculosis.
Fig. 2
Fig. 2. Historical phylogeny of BCG vaccine strains. Continuous passage of the original strain attenuated by Calmette and Guérin resulted in a number of diverse daughter strains.
Loss of the genomic region of difference 1 (RD1) generated the early Bacillus Calmette–Guérin (BCG) strains (groups I and II). Late strains (groups III and IV) were subsequently generated by deletion of RD2. Adapted from Brosch et al., PNAS. Copyright (2007) National Academy of Sciences, USA.
Fig. 3
Fig. 3. Proposed model of trained immunity.
Innate immune responses during and after an infectious episode can lead to immunological programming, and a heightened immunity (trained immunity) that might translate into decreased susceptibility to (unrelated) secondary infections. Adapted from O’Neill and Netea, Springer Nature Limited.
Fig. 4
Fig. 4. Summary of recommendations for intravesical BCG vaccine use in NMIBC in the COVID-19 era.
BCG, Bacillus Calmette–Guérin; EAU, European Association of Urology; NMIBC, non-muscle-invasive bladder cancer.
See this image and copyright information in PMC

References

    1. World Health Organization. BCG vaccine. WHOhttps://www.who.int/biologicals/areas/vaccines/bcg/en/ (2018). - PubMed
    1. Trunz BB, Fine P, Dye C. Effect of BCG vaccination on childhood tuberculous meningitis and military tuberculosis worldwide: a meta-analysis and assessment of cost-effectiveness. Lancet. 2006;367:1173–1180. doi: 10.1016/S0140-6736(06)68507-3. - DOI - PubMed
    1. Babjuk M, et al. EAU Guidelines on non-muscle-invasive bladder cancer (TaT1 and carcinoma in situ) — 2019 update. Eur. Urol. 2019;75:639–657. doi: 10.1016/j.eururo.2019.08.016. - DOI - PubMed
    1. World Health Organization. Coronavirus disease (COVID-19) pandemic. WHOhttps://www.who.int/emergencies/diseases/novel-coronavirus-2019 (2020).
    1. Dong E, Du H, Gardner L. An interactive web-based dashboard to trace COVID-19 in real time. Lancet. 2020;20:533–534. doi: 10.1016/S1473-3099(20)30120-1. - DOI - PMC - PubMed