Immune Tolerance Network

项目概要/摘要 BCG可以诱导先天免疫系统的表观遗传变化，具有非特异性记忆特征， 称为“训练免疫”，与对异源感染的增强免疫应答有关， 疫苗。我们假设卡介苗接种诱导的免疫增强将为 高风险个体对抗COVID-19和其他病毒性呼吸道感染。将评估这一假设 通过进行BCG东京的II期双盲、随机、安慰剂（媒介物）对照临床试验， 172-1（BCG-日本）疫苗用于预防医护人员（高危医护人员）的COVID-19 感染日本卡介苗是最有效的卡介苗制剂之一，表现出相对较高的免疫原性。 微生物活力和人类先天免疫激活，并提供强大的保护，防止结核病和多种 脱靶感染本研究将检验以下假设： 高感染风险将增强先天抗病毒免疫力，以降低SARS-CoV-2感染的风险，和/或 COVID-19的严重程度。将随机抽取2,800名符合条件的志愿保健工作者， 分配到安慰剂疫苗接种或BCG-日本，在Brigham & Women's Hospital进行， 4个临床试验机构。将对受试者进行为期两年的监测，评估病毒性疾病， SARS-CoV-2的血清学和分子监测。一部分科目将使用 一套系统生物学分析，将与临床数据相结合，以深入了解 BCG对与SARS-CoV-2感染和/或COVID发病率或严重程度相关的人体免疫力的影响。整体 这一方面将提供关于BCG如何重塑人类血液和鼻粘膜的信息 可能与SARS-CoV-2感染和/或发病率相关的保护作用 和COVID的严重性。

Project Summary/ Abstract BCG can induce epigenetic changes in the innate immune system with non-specific memory characteristics, termed `trained immunity', associated with enhanced immune responses to heterologous infections and vaccines. We hypothesize that the enhanced immunity induced by BCG vaccination will provide protection for high-risk individuals against COVID-19 and other viral respiratory infections. This hypothesis will be assessed by conducting a Phase II double blind, randomized, placebo (vehicle)-controlled clinical trial of BCG Tokyo 172-1 (BCG-Japan) vaccine for the prevention of COVID-19 in healthcare workers (HCWs at high-risk for infection. BCG-Japan is one of the most potent formulations of BCG vaccine demonstrating relatively high microbial viability and human innate immune activation, and offering robust protection against TB and multiple off-target infections. This study will test the hypothesis that administration of BCG-Japan vaccine to HCWs at high-risk for infection will enhance innate antiviral immunity to reduce the risk for SARS-CoV-2 .infection and/or severity of COVID-19. Two thousand and eight hundred (2,800) eligible volunteer HCWs will be randomly assigned to either a placebo vaccination or BCG-Japan, conducted at Brigham & Women's Hospital and up to four additional clinical sites. Subjects will be monitored for two years with assessments for viral illness and serological and molecular monitoring for SARS-CoV-2. A subset of subjects will be intensively studied using a suite of systems biology analyses, which will be integrated with clinical data to gain insight into the impact of BCG on human immunity in relation to SARS-CoV-2 infection and/or incidence or severity of COVID. Overall this aspect will provide information regarding how BCG may reshape the human blood and nasal mucosal compartments in a manner that may correlate with protection against SARS-CoV-2 infection and/or incidence and severity of COVID.