Nicole L Messina, Susie Germano, Rebecca McElroy, Rajeev Rudraraju, Rhian Bonnici, Laure F Pittet, Melanie R Neeland, Suellen Nicholson, Kanta Subbarao, Nigel Curtis, the BRACE trial
{"title":"卡介苗-谷氨酰胺芽孢杆菌疫苗对SARS-CoV-2免疫应答的脱靶效应:对预防严重COVID-19的影响","authors":"Nicole L Messina, Susie Germano, Rebecca McElroy, Rajeev Rudraraju, Rhian Bonnici, Laure F Pittet, Melanie R Neeland, Suellen Nicholson, Kanta Subbarao, Nigel Curtis, the BRACE trial","doi":"10.1002/cti2.1387","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background and objectives</h3>\n \n <p>Because of its beneficial off-target effects against non-mycobacterial infectious diseases, bacillus Calmette–Guérin (BCG) vaccination might be an accessible early intervention to boost protection against novel pathogens. Multiple epidemiological studies and randomised controlled trials (RCTs) are investigating the protective effect of BCG against coronavirus disease 2019 (COVID-19). Using samples from participants in a placebo-controlled RCT aiming to determine whether BCG vaccination reduces the incidence and severity of COVID-19, we investigated the immunomodulatory effects of BCG on <i>in vitro</i> immune responses to SARS-CoV-2.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>This study used peripheral blood taken from participants in the multicentre RCT and BCG vaccination to reduce the impact of COVID-19 on healthcare workers (BRACE trial). The whole blood taken from BRACE trial participants was stimulated with γ-irradiated SARS-CoV-2-infected or mock-infected Vero cell supernatant. Cytokine responses were measured by multiplex cytokine analysis, and single-cell immunophenotyping was made by flow cytometry.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>BCG vaccination, but not placebo vaccination, reduced SARS-CoV-2-induced secretion of cytokines known to be associated with severe COVID-19, including IL-6, TNF-α and IL-10. In addition, BCG vaccination promoted an effector memory phenotype in both CD4<sup>+</sup> and CD8<sup>+</sup> T cells, and an activation of eosinophils in response to SARS-CoV-2.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>The immunomodulatory signature of BCG’s off-target effects on SARS-CoV-2 is consistent with a protective immune response against severe COVID-19.</p>\n </section>\n </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"11 4","pages":""},"PeriodicalIF":4.6000,"publicationDate":"2022-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1387","citationCount":"16","resultStr":"{\"title\":\"Off-target effects of bacillus Calmette–Guérin vaccination on immune responses to SARS-CoV-2: implications for protection against severe COVID-19\",\"authors\":\"Nicole L Messina, Susie Germano, Rebecca McElroy, Rajeev Rudraraju, Rhian Bonnici, Laure F Pittet, Melanie R Neeland, Suellen Nicholson, Kanta Subbarao, Nigel Curtis, the BRACE trial\",\"doi\":\"10.1002/cti2.1387\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Background and objectives</h3>\\n \\n <p>Because of its beneficial off-target effects against non-mycobacterial infectious diseases, bacillus Calmette–Guérin (BCG) vaccination might be an accessible early intervention to boost protection against novel pathogens. Multiple epidemiological studies and randomised controlled trials (RCTs) are investigating the protective effect of BCG against coronavirus disease 2019 (COVID-19). Using samples from participants in a placebo-controlled RCT aiming to determine whether BCG vaccination reduces the incidence and severity of COVID-19, we investigated the immunomodulatory effects of BCG on <i>in vitro</i> immune responses to SARS-CoV-2.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>This study used peripheral blood taken from participants in the multicentre RCT and BCG vaccination to reduce the impact of COVID-19 on healthcare workers (BRACE trial). The whole blood taken from BRACE trial participants was stimulated with γ-irradiated SARS-CoV-2-infected or mock-infected Vero cell supernatant. Cytokine responses were measured by multiplex cytokine analysis, and single-cell immunophenotyping was made by flow cytometry.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>BCG vaccination, but not placebo vaccination, reduced SARS-CoV-2-induced secretion of cytokines known to be associated with severe COVID-19, including IL-6, TNF-α and IL-10. In addition, BCG vaccination promoted an effector memory phenotype in both CD4<sup>+</sup> and CD8<sup>+</sup> T cells, and an activation of eosinophils in response to SARS-CoV-2.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>The immunomodulatory signature of BCG’s off-target effects on SARS-CoV-2 is consistent with a protective immune response against severe COVID-19.</p>\\n </section>\\n </div>\",\"PeriodicalId\":152,\"journal\":{\"name\":\"Clinical & Translational Immunology\",\"volume\":\"11 4\",\"pages\":\"\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2022-04-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1387\",\"citationCount\":\"16\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical & Translational Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/cti2.1387\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical & Translational Immunology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/cti2.1387","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Off-target effects of bacillus Calmette–Guérin vaccination on immune responses to SARS-CoV-2: implications for protection against severe COVID-19
Background and objectives
Because of its beneficial off-target effects against non-mycobacterial infectious diseases, bacillus Calmette–Guérin (BCG) vaccination might be an accessible early intervention to boost protection against novel pathogens. Multiple epidemiological studies and randomised controlled trials (RCTs) are investigating the protective effect of BCG against coronavirus disease 2019 (COVID-19). Using samples from participants in a placebo-controlled RCT aiming to determine whether BCG vaccination reduces the incidence and severity of COVID-19, we investigated the immunomodulatory effects of BCG on in vitro immune responses to SARS-CoV-2.
Methods
This study used peripheral blood taken from participants in the multicentre RCT and BCG vaccination to reduce the impact of COVID-19 on healthcare workers (BRACE trial). The whole blood taken from BRACE trial participants was stimulated with γ-irradiated SARS-CoV-2-infected or mock-infected Vero cell supernatant. Cytokine responses were measured by multiplex cytokine analysis, and single-cell immunophenotyping was made by flow cytometry.
Results
BCG vaccination, but not placebo vaccination, reduced SARS-CoV-2-induced secretion of cytokines known to be associated with severe COVID-19, including IL-6, TNF-α and IL-10. In addition, BCG vaccination promoted an effector memory phenotype in both CD4+ and CD8+ T cells, and an activation of eosinophils in response to SARS-CoV-2.
Conclusions
The immunomodulatory signature of BCG’s off-target effects on SARS-CoV-2 is consistent with a protective immune response against severe COVID-19.
期刊介绍：
Clinical & Translational Immunology is an open access, fully peer-reviewed journal devoted to publishing cutting-edge advances in biomedical research for scientists and physicians. The Journal covers fields including cancer biology, cardiovascular research, gene therapy, immunology, vaccine development and disease pathogenesis and therapy at the earliest phases of investigation.
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