COVID-19 and Beyond: Exploring Public Health Benefits from Non-Specific Effects of BCG Vaccination

Koster, Kent; Webb, Hilary L.; Cirillo, Jeffrey D.

doi:10.3390/microorganisms9102120

Cited by 5 publications

(7 citation statements)

References 168 publications

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“…This includes a multicenter US study: ClinicalTrials.gov Identifier: NCT04348370. The large data sets associated with COVID-19 vaccines will undoubtedly be mined for years to come including the role that BCG may have had with COVID-19 [47].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of BCG Vaccination and Plasma Amyloid: A Prospective, Pilot Study with Implications for Alzheimer’s Disease

et al. 2022

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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.

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Section: Discussionmentioning

confidence: 99%

Evaluation of BCG Vaccination and Plasma Amyloid: A Prospective, Pilot Study with Implications for Alzheimer’s Disease

et al. 2022

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“…50 Other studies found that increased rates of BCG vaccination by country were correlated with slower rates of COVID-19 infection in the population, although many factors may confound the relationship. 51 Of note, a heat-killed strain of Mycobacterium (Mycobacterium w.) can be used as an immunomodulator and was injected as adjuvant therapy for COVID-19 infection with some associated clinical benefit. 52 However, cutaneous infection and ulceration was a common side effect.…”

Section: Mycobacteria and Covid-19mentioning

confidence: 99%

Dermatology practice updates in mycobacterial disease

Barker,

Alshaikh,

Elston

2023

Int J Dermatology

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Atypical mycobacterial infections are commonly acquired through exposure to water, and tuberculosis remains highly endemic in many parts of the world. In this era of global connection, travel, and immigration, it is more important than ever to maintain a high index of suspicion for infection from cutaneous tuberculosis and atypical mycobacteria. Epidemics related to surgical procedures have been related to inadequate sterilization, as almost 50% of public water supplies harbor mycobacteria. Improved diagnostic techniques for these microbes, including Auramine–Rhodamine staining and rapid detection of mycobacteria and drug susceptibilities through PCR and MALDI‐TOF, have improved detection and treatment outcomes. Given an increasing number of patients on immunosuppressive therapies, clinicians must remain vigilant.

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“…For instance, the current BCG Pasteur differs from the original Pasteur strain by polymorphisms and deletions. BCG strains are used both as a vaccine to prevent TB and as an immunotherapy of bladder cancer [57,121]. In addition, there is active research on the use of BCG to treat other cancers and non-infectious diseases, such as autoimmune disorders and type I diabetes [122].…”

Section: Mycobacterium Bovis Bcgmentioning

confidence: 99%

“…Subsequent observational studies in children in West Africa demonstrated that BCG vaccination decreases morbidity due to infections other than TB, including malaria [54,55]. Very recently, epidemiological studies indicated that TI induced by BCG could be protective against the development of severe coronavirus disease 2019 in humans [56,57]. Strikingly, studies performed in the 1970's showed that BCG inoculation protects mice against lethal experimental infection with B. microti and Plasmodium berghei [58,59].…”

Section: Introductionmentioning

confidence: 99%

Harnessing Mycobacterium bovis BCG Trained Immunity to Control Human and Bovine Babesiosis

et al. 2022

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Babesiosis is a disease caused by tickborne hemoprotozoan apicomplexan parasites of the genus Babesia that negatively impacts public health and food security worldwide. Development of effective and sustainable vaccines against babesiosis is currently hindered in part by the absence of definitive host correlates of protection. Despite that, studies in Babesia microti and Babesia bovis, major causative agents of human and bovine babesiosis, respectively, suggest that early activation of innate immune responses is crucial for vertebrates to survive acute infection. Trained immunity (TI) is defined as the development of memory in vertebrate innate immune cells, allowing more efficient responses to subsequent specific and non-specific challenges. Considering that Mycobacterium bovis bacillus Calmette-Guerin (BCG), a widely used anti-tuberculosis attenuated vaccine, induces strong TI pro-inflammatory responses, we hypothesize that BCG TI may protect vertebrates against acute babesiosis. This premise is supported by early investigations demonstrating that BCG inoculation protects mice against experimental B. microti infection and recent observations that BCG vaccination decreases the severity of malaria in children infected with Plasmodium falciparum, a Babesia-related parasite. We also discuss the potential use of TI in conjunction with recombinant BCG vaccines expressing Babesia immunogens. In conclusion, by concentrating on human and bovine babesiosis, herein we intend to raise awareness of BCG TI as a strategy to efficiently control Babesia infection.

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COVID-19 and Beyond: Exploring Public Health Benefits from Non-Specific Effects of BCG Vaccination

Cited by 5 publications

References 168 publications

Evaluation of BCG Vaccination and Plasma Amyloid: A Prospective, Pilot Study with Implications for Alzheimer’s Disease

Evaluation of BCG Vaccination and Plasma Amyloid: A Prospective, Pilot Study with Implications for Alzheimer’s Disease

Dermatology practice updates in mycobacterial disease

Harnessing Mycobacterium bovis BCG Trained Immunity to Control Human and Bovine Babesiosis

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