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BCG-induced trained immunity: can it offer protection against COVID-19?

Published on May 11, 2020in Nature Reviews Immunology44.019
· DOI :10.1038/S41577-020-0337-Y
Luke A. J. O'Neill109
Estimated H-index: 109
(Trinity College, Dublin),
Mihai G. Netea1
Estimated H-index: 1
(University of Bonn)
Sources
Abstract
Bacillus Calmette–Guerin (BCG) vaccination has been reported to decrease susceptibility to respiratory tract infections, an effect proposed to be mediated by the general long-term boosting of innate immune mechanisms, also termed trained immunity. Here, we discuss the non-specific beneficial effects of BCG against viral infections and whether this vaccine may afford protection to COVID-19. Could the BCG vaccine be used to bridge the gap until a specific COVID-19 vaccine is developed? Luke O’Neill and Mihai Netea discuss the science behind this approach.
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  • References (16)
  • Citations (8)
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References16
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#1Mayda Gursel (METU: Middle East Technical University)H-Index: 27
#2Ihsan Gursel (Bilkent University)H-Index: 34
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#1Puja Mehta (UCL: University College London)H-Index: 2
#2Daniel F. McAuley ('QUB': Queen's University Belfast)H-Index: 51
Last. Jessica Manson (UCLH: University College Hospital)H-Index: 11
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#1Chao-Lin Huang (Wuhan Jinyintan Hospital)H-Index: 2
#2Ya-min Wang (China-Japan Friendship Hospital)H-Index: 1
Last. Gu X (China-Japan Friendship Hospital)H-Index: 1
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A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generati...
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#1Simone J.C.F.M. Moorlag (Radboud University Nijmegen)H-Index: 6
#2Rob J.W. Arts (Radboud University Nijmegen)H-Index: 21
Last. Mihai G. Netea (University of Bonn)H-Index: 115
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Abstract Background Some strains of Bacillus Calmette–Guerin (BCG) vaccine not only confer protection against disseminated forms of tuberculosis, but also reduce all-cause mortality by the induction of protection against infections with non-related pathogens. Objectives We review evidence for non-specific protection induced by BCG vaccination against viral infections, discuss possible mechanisms of action, and summarize implications for vaccination policies and vaccine discovery. Sources Relevan...
32 CitationsSource
#1Elisa NemesH-Index: 11
#2Hennie GeldenhuysH-Index: 20
Last. Mark HatherillH-Index: 3
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Abstract Background Recent Mycobacterium tuberculosis infection confers a predisposition to the development of tuberculosis disease, the leading killer among global infectious diseases. H4:IC31, a candidate subunit vaccine, has shown protection against tuberculosis disease in preclinical models, and observational studies have indicated that primary bacille Calmette–Guerin (BCG) vaccination may offer partial protection against infection. Methods In this phase 2 trial, we randomly assigned 990 ado...
73 CitationsSource
#1Rob J.W. Arts (Radboud University Nijmegen)H-Index: 21
#2Simone J.C.F.M. Moorlag (Radboud University Nijmegen)H-Index: 6
Last. Mihai G. Netea (University of Bonn)H-Index: 115
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Summary The tuberculosis vaccine bacillus Calmette-Guerin (BCG) has heterologous beneficial effects against non-related infections. The basis of these effects has been poorly explored in humans. In a randomized placebo-controlled human challenge study, we found that BCG vaccination induced genome-wide epigenetic reprograming of monocytes and protected against experimental infection with an attenuated yellow fever virus vaccine strain. Epigenetic reprogramming was accompanied by functional change...
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#2Leo A. B. Joosten (Radboud University Nijmegen)H-Index: 101
Last. Ramnik J. Xavier (Broad Institute)H-Index: 114
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BACKGROUND Host immune responses are classically divided into innate immune responses, which react rapidly and nonspecifically upon encountering a pathogen, and adaptive immune responses, which are slower to develop but are specific and build up immunological memory. The dogma that only adaptive immunity can build immunological memory has recently been challenged by studies showing that innate immune responses in plants and invertebrates (organisms lacking adaptive immune responses) can mount re...
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Adaptive features of innate immunity, recently described as “trained immunity,” have been documented in plants, invertebrate animals, and mice, but not yet in humans. Here we show that bacille Calmette-Guerin (BCG) vaccination in healthy volunteers led not only to a four- to sevenfold increase in the production of IFN-γ, but also to a twofold enhanced release of monocyte-derived cytokines, such as TNF and IL-1β, in response to unrelated bacterial and fungal pathogens. The enhanced function of ci...
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Background. Observational studies have suggested that BCG may have nonspecific beneficial effects on survival. Low-birth-weight (LBW) children are not given BCG at birth in Guinea-Bissau; we conducted a randomized trial of BCG at birth (early BCG) vs delayed BCG. Methods. In the period 2004-2008 we recruited 2320 LBW children in Bissau. The children were visited at home at 2, 6, and 12 months of age. With a pretrial infant mortality of 250 per 1000, we hypothesized a 25% reduction in infant mort...
216 CitationsSource
#1WardhanaH-Index: 4
#2E A DatauH-Index: 5
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SARS-CoV-2 infection can cause severe disease for which currently no specific therapy is available. The use of hydroxychloroquine to prevent or treat SARS-CoV-2 infection is controversial and its mode of action poorly understood. We demonstrate that hydroxychloroquine inhibits trained immunity at the functional and epigenetic level and is accompanied by profound changes in the cellular lipidome as well as reduced expression of interferon-stimulated genes. Trained immunity comprises a functional ...
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