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Microorganisms
Special Issues
Non-Canonical Uses for BCG Vaccine
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Non-Canonical Uses for BCG Vaccine

A special issue of Microorganisms (ISSN 2076-2607). This special issue belongs to the section "Antimicrobial Agents and Resistance".

Deadline for manuscript submissions: closed (4 July 2022) | Viewed by 15464

Special Issue Editors

Dr. Edward D. Chan

E-Mail Website
Guest Editor
Department of Academic Affairs, National Jewish Health, Denver, CO, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Anschutz Medical Campus, Aurora, Rocky Mountain Regional Veterans Affairs Medical Center, Aurora, CO, USA
Interests: non-tuberculous mycobacteria (NTM); tuberculosis (TB)
Dr. Coad Thomas Dow

E-Mail Website
Guest Editor
McPherson Eye Research Institute, University of Wisconsin, Madison, WI, USA
Interests: autoimmune disease; Mycobacterium paratuberculosis; zoonosis

Special Issue Information

Dear Colleagues,

BCG vaccination is being used and studied in a wide variety of human maladies beyond its original purpose: to lessen risk of tuberculosis.  BCG is being tested in mycobacterial infection other than TB; moreover, BCG is being studied for diabetes, multiple sclerosis, Alzheimer’s disease, and COVID-19. This Special Issue will provide a platform for discussion of BCG and its plausible mechanisms for favorably impacting a variety of infectious, autoimmune, and neurodegenerative diseases.

Dr. Edward D. Chan
Dr. Coad Dow
Guest Editors

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Keywords

  • Bacillus Calmette Guerin (BCG)
  • non-tuberculous mycobacteria (NTM)
  • tuberculosis
  • diabetes
  • multiple sclerosis
  • Alzheimer’s disease
  • Parkinson’s disease
  • COVID19
  • non-canonical
  • off-target
  • trained immunity
  • aerobic glycolysis
  • cervical lymphadenitis
  • Mycobacterium avium ss. paratuberculosis

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Published Papers (3 papers)

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Research

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12 pages, 2952 KiB  
Article
Evaluation of BCG Vaccination and Plasma Amyloid: A Prospective, Pilot Study with Implications for Alzheimer’s Disease
by Coad Thomas Dow, Charles L. Greenblatt, Edward D. Chan and Jordan F. Dow
Microorganisms 2022, 10(2), 424; https://doi.org/10.3390/microorganisms10020424 - 12 Feb 2022
Cited by 11 | Viewed by 4437
Abstract
BCG vaccine has been used for 100 years to prevent tuberculosis. Not all countries, including the United States, adopted the initial World Health Organization recommendation to use BCG. Moreover, many Western countries that had routinely used BCG have discontinued its use. Recent population [...] Read more.
BCG vaccine has been used for 100 years to prevent tuberculosis. Not all countries, including the United States, adopted the initial World Health Organization recommendation to use BCG. Moreover, many Western countries that had routinely used BCG have discontinued its use. Recent population studies demonstrate lower prevalence of Alzheimer’s disease (AD) in countries with high BCG coverage. Intravesicular instillation of BCG is also used to treat bladder cancer that has not invaded the bladder muscle wall and has been shown to reduce recurrence. Several retrospective studies of bladder cancer patients demonstrated that BCG treatment was associated with a significantly reduced risk of developing AD. Plasma amyloid β assessment has become a fertile area of study for an AD biomarker that is predictive of a positive amyloid PET scan. Mass spectrometry-based plasma amyloid 42/40 ratio has proven to be accurate and robust, and when combined with age and ApoE, is shown to accurately predict current and future brain amyloid status. These parameters, amyloid 42/40 ratio, age and ApoE genotype are incorporated into an Amyloid Probability Score (APS)–a score that identifies low, intermediate or high risk of having a PET scan positive for cerebral amyloid. Community recruitment was used for this open-label pilot study. Forty-nine BCG-naïve, immunocompetent individuals completed our study: prior to BCG prime and boost, as determined by the APS, 34 had low risk (APS 0–35), 5 had intermediate risk (APS 36–57) and 10 had high risk (APS 58–100). The APS range for the participant group was 0 to 94. Follow-up plasma amyloid testing 9 months after vaccination revealed a reduction in the APS in all the risk groups: low risk group (p = 0. 37), intermediate risk group (p = 0.13) and the high-risk group (statistically significant, p = 0.016). Greater benefit was seen in younger participants and those with the highest risk. The small number of participants and the nascent status of plasma amyloid testing will rightfully temper embracement of these results. However, both the favorable direction of change after BCG as well as the utility of the APS—a valuable surrogate AD biomarker—may prompt a definitive large-scale multicenter investigation of BCG and AD risk as determined by plasma amyloid peptide ratios and APS. Full article
(This article belongs to the Special Issue Non-Canonical Uses for BCG Vaccine)
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Review

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11 pages, 1201 KiB  
Review
BCG Vaccine—The Road Not Taken
by Coad Thomas Dow and Laith Kidess
Microorganisms 2022, 10(10), 1919; https://doi.org/10.3390/microorganisms10101919 - 27 Sep 2022
Cited by 3 | Viewed by 2771
Abstract
The Bacillus Calmette-Guérin (BCG) vaccine has been used for over one hundred years to protect against the most lethal infectious agent in human history, tuberculosis. Over four billion BCG doses have been given and, worldwide, most newborns receive BCG. A few countries, including [...] Read more.
The Bacillus Calmette-Guérin (BCG) vaccine has been used for over one hundred years to protect against the most lethal infectious agent in human history, tuberculosis. Over four billion BCG doses have been given and, worldwide, most newborns receive BCG. A few countries, including the United States, did not adopt the WHO recommendation for routine use of BCG. Moreover, within the past several decades, most of Western Europe and Australia, having originally employed routine BCG, have discontinued its use. This review article articulates the impacts of those decisions. The suggested consequences include increased tuberculosis, increased infections caused by non-tuberculous mycobacteria (NTM), increased autoimmune disease (autoimmune diabetes and multiple sclerosis) and increased neurodegenerative disease (Parkinson’s disease and Alzheimer’s disease). This review also offers an emerged zoonotic pathogen, Mycobacteriumavium ss. paratuberculosis (MAP), as a mostly unrecognized NTM that may have a causal role in some, if not all, of these diseases. Current clinical trials with BCG for varied infectious, autoimmune and neurodegenerative diseases have brought this century-old vaccine to the fore due to its presumed immuno-modulating capacity. With its historic success and strong safety profile, the new and novel applications for BCG may lead to its universal use–putting the Western World back onto the road not taken. Full article
(This article belongs to the Special Issue Non-Canonical Uses for BCG Vaccine)
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26 pages, 985 KiB  
Review
COVID-19 and Beyond: Exploring Public Health Benefits from Non-Specific Effects of BCG Vaccination
by Kent J. Koster, Hilary L. Webb and Jeffrey D. Cirillo
Microorganisms 2021, 9(10), 2120; https://doi.org/10.3390/microorganisms9102120 - 9 Oct 2021
Cited by 5 | Viewed by 7260
Abstract
Bacille Calmette–Guérin (BCG) vaccination, widely used throughout the world to protect against infant tuberculous meningitis and miliary tuberculosis (TB), can provide broad non-specific protection against infectious respiratory diseases in certain groups. Interest in BCG has seen a resurgence within the scientific community as [...] Read more.
Bacille Calmette–Guérin (BCG) vaccination, widely used throughout the world to protect against infant tuberculous meningitis and miliary tuberculosis (TB), can provide broad non-specific protection against infectious respiratory diseases in certain groups. Interest in BCG has seen a resurgence within the scientific community as the mechanisms for non-specific protection have begun to be elucidated. The impact of the COVID-19 pandemic on nearly every aspect of society has profoundly illustrated the pressure that respiratory infections can place on a national healthcare system, further renewing interest in BCG vaccination as a public health policy to reduce the burden of those illnesses. However, the United States does not recommend BCG vaccination due to its variable effectiveness against adult TB, the relatively low risk of Mycobacterium tuberculosis infection in most of the United States, and the vaccine’s interference with tuberculin skin test reactivity that complicates TB screening. In this review, we explore the broad immune training effects of BCG vaccination and literature on the effects of BCG vaccination on COVID-19 spread, disease severity, and mortality. We further discuss barriers to scheduled BCG vaccination in the United States and how those barriers could potentially be overcome. Full article
(This article belongs to the Special Issue Non-Canonical Uses for BCG Vaccine)
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