Messina Nicole L, Germano Susie, McElroy Rebecca, Rudraraju Rajeev, Bonnici Rhian, Pittet Laure F, Neeland Melanie R, Nicholson Suellen, Subbarao Kanta, Curtis Nigel
Infectious Diseases Group, Infection and Immunity Theme Murdoch Children's Research Institute Parkville VIC Australia.
Department of Paediatrics The University of Melbourne Parkville VIC Australia.
Clin Transl Immunology. 2022 Apr 22;11(4):e1387. doi: 10.1002/cti2.1387. eCollection 2022.
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 immune responses to SARS-CoV-2.
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.
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.
The immunomodulatory signature of BCG's off-target effects on SARS-CoV-2 is consistent with a protective immune response against severe COVID-19.
由于卡介苗（BCG）对非分枝杆菌感染性疾病具有有益的非靶向效应，BCG疫苗接种可能是一种可及的早期干预措施，以增强对新型病原体的防护。多项流行病学研究和随机对照试验（RCT）正在调查BCG对2019冠状病毒病（COVID-19）的保护作用。我们利用一项安慰剂对照RCT参与者的样本，旨在确定BCG疫苗接种是否能降低COVID-19的发病率和严重程度，研究了BCG对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）免疫反应的免疫调节作用。
本研究使用了多中心RCT参与者的外周血以及BCG疫苗接种，以降低COVID-19对医护人员的影响（BRACE试验）。用经γ射线照射的感染SARS-CoV-2或模拟感染的Vero细胞上清液刺激BRACE试验参与者采集的全血。通过多重细胞因子分析测量细胞因子反应，并通过流式细胞术进行单细胞免疫表型分析。
BCG疫苗接种而非安慰剂接种，减少了SARS-CoV-2诱导的已知与严重COVID-19相关的细胞因子分泌，包括白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和白细胞介素-10（IL-10）。此外，BCG疫苗接种促进了CD4和CD8 T细胞的效应记忆表型，并促进了嗜酸性粒细胞对SARS-CoV-2的激活。
BCG对SARS-CoV-2的非靶向效应的免疫调节特征与针对严重COVID-19的保护性免疫反应一致。
