The duration of protection of school-aged BCG vaccination in England: a population-based case–control study

Mangtani, Punam; Nguipdop-Djomo, Patrick; Keogh, Ruth H.; Sterne, Jonathan A C; Abubakar, Ibrahim; Smith, P. G.; Fine, Paul E. M.; Vynnycky, Emilia; Watson, John M.; Elliman, David; Lipman, Marc; Rodrigues, Laura C.

doi:10.1093/ije/dyx141

Cited by 48 publications

(39 citation statements)

References 20 publications

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“…This latter finding could have implications for understanding different levels of protection from BCG across populations with varying intensity of Mtb transmission, protection being weakest in high-TB-burden settings (121). In addition, the study by Verrall et al found evidence of BCG protection against infection up until the age of 30 years, which is consistent with recent studies suggesting that BCG protection against TB disease lasts at least 20 years when given at birth or at school age (122,123).…”

Section: Insights Gained From Bcg Vaccination In Human Studiessupporting

confidence: 65%

Targeting innate immunity for tuberculosis vaccination

Khader¹,

Divangahi²,

Hanekom³

et al. 2019

Journal of Clinical Investigation

107

108

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Section: Insights Gained From Bcg Vaccination In Human Studiessupporting

confidence: 65%

Targeting innate immunity for tuberculosis vaccination

Khader¹,

Divangahi²,

Hanekom³

et al. 2019

Journal of Clinical Investigation

107

108

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“…Supporting evidence for this hypothesis is found in the literature [36] indicating that the protective effects of the BCG against TB, can last from 15 to 60 years after vaccination, with longer lasting effects when the vaccine is administered during the rst year of life. [32] A recent study indicated that "school-aged BCG vaccination offered moderate protection against tuberculosis for at least 20 years, which is much longer than previously thought" [32].…”

Section: Discussionmentioning

confidence: 66%

A Systems Biology Workflow for Drug and Vaccine Repurposing: Identifying Small-molecule BCG Mimics to Prevent COVID-19 Mortality

Hajjo

Tropsha

2020

Preprint

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Purpose: Coronavirus disease 2019 (COVID-19) is expected to continue to cause worldwide fatalities until the World population develops ‘herd immunity’, or until a vaccine is developed and used as a prevention. However, the vaccine may prove ineffective due to rapid changes in viral antigenic determinants. Bacillus Calmette–Guérin (BCG) vaccine has been recognized for its off-target beneficial effects on the immune system, therefore, can be exploited to boast immunity and protect from emerging novel viruses.Methods: We developed a systems biology workflow capable of identifying small-molecule antiviral drugs and vaccines that can boast immunity and impact a wide variety of viral disease pathways to protect from the fatal consequences of emerging viruses. Results: We show that BCG affect the production and maturation of naïve T cells, which results in enhanced long-lasting trained innate immune responses to tackle novel viruses. Our workflow identified small-molecule BCG mimics, including antiviral drugs such as raltegravir and lopinavir as high confidence hits. Strikingly, top hits emetine and lopinavir were validated to inhibit the growth of SARS-CoV-2 in vitro.Conclusions: Our results provide systems biology support for using BCG and small-molecule BCG mimics as a protection measure from the lethal consequences of emergent viruses including SARS-CoV-2.

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“…The impact of infant BCG vaccination on pulmonary disease in adolescence and adults, which is responsible for driving the cycle of Mtb transmission in high TB incidence countries, is reduced by the fact that efficacy of infant BCG vaccination is not durable into adulthood (Sterne et al, 1998). Systematic reviews illustrate that, except for a handful of studies in low TB burden settings (Aronson et al, 2004;Barreto et al, 2005;Mangtani et al, 2018), BCG-induced protection wanes to zero by 10-15 years after vaccination (Abubakar et al, 2013;Sterne et al, 1998).…”

Section: Pre-exposure Approaches To Infant Vaccinationmentioning

confidence: 99%

Clinical Development of New TB Vaccines: Recent Advances and Next Steps

2020

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Mycobacterium tuberculosis (Mtb) kills more people worldwide than any single infectious pathogen, yet the only vaccine licensed against tuberculosis, Bacille Calmette Guerin (BCG) is approaching its centenary. Two recent advances in clinical tuberculosis vaccine development have invigorated the field. BCG revaccination of interferon-gamma release assay (IGRA) negative adolescents provided 45% protection against sustained Mtb infection defined by IGRA conversion; and the protein-subunit vaccine M72/AS01 E provided 50% protection against progression from Mtb infection to tuberculosis disease in IGRA-positive adults. These findings provide encouraging evidence for pre-exposure and post-exposure approaches to vaccination against tuberculosis, both of which may be necessary to rapidly interrupt the cycle of Mtb transmission and sustain long-term impact on global tuberculosis control. New trials are needed to demonstrate efficacy of M72/AS01 E with greater precision, in a wider age range, in diverse epidemic settings, and in populations that include Mtb-uninfected and HIV-infected persons. Modeling the impact of mass campaigns with M72/AS01 E and other fast-follower vaccine candidates will be crucial to make the use case and demonstrate public health value for TB endemic countries. The size and scope of the next generation of efficacy trials, and the need to expand and accelerate the existing clinical development pipeline, will require public and private consortium funding and concerted political will.

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The duration of protection of school-aged BCG vaccination in England: a population-based case–control study

Abstract: School-aged BCG vaccination offered moderate protection against tuberculosis for at least 20 years, which is longer than previously thought. This has implications for assessing the cost-effectiveness of BCG vaccination and when evaluating new TB vaccines.

Cited by 48 publications

References 20 publications

Targeting innate immunity for tuberculosis vaccination

Targeting innate immunity for tuberculosis vaccination

A Systems Biology Workflow for Drug and Vaccine Repurposing: Identifying Small-molecule BCG Mimics to Prevent COVID-19 Mortality

Clinical Development of New TB Vaccines: Recent Advances and Next Steps

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