Immune Tolerance Network

项目摘要/摘要 卡介苗可以诱导具有非特异性记忆特征的先天免疫系统的表观遗传变化， 称为“训练免疫”，与增强对异源感染的免疫反应有关 疫苗。我们推测，接种卡介苗引起的增强免疫力将为 新冠肺炎和其他病毒性呼吸道感染的高危人群。这一假设将得到评估。 通过对东京卡介苗进行II期双盲、随机、安慰剂(载体)对照临床试验 用于预防医护人员新冠肺炎的疫苗(卡介苗-日本) 感染。日本卡介苗是最有效的卡介苗配方之一，表现出相对较高的 微生物生存能力和人类天然免疫激活，并提供强大的保护，以防止结核病和 非目标感染。这项研究将检验这样一种假设，即向卫生工作者接种卡介苗 感染高危人群可增强先天抗病毒免疫，降低感染和/或感染SARS-CoV-2的风险 新冠肺炎的严重程度。2,800(2,800)名符合资格的志愿卫生福利院将随机抽取 被分配到安慰剂疫苗接种或BCG-日本，在布里格姆妇女医院进行，最多 增加了四个临床站点。受试者将接受为期两年的监测，评估病毒疾病和 SARS-CoV-2的血清学和分子监测。主题的子集将使用 一套系统生物学分析，将与临床数据相结合，以深入了解 卡介苗对人类免疫与SARS-CoV-2感染和/或COVID发病率或严重性的关系。总括 这方面将提供有关卡介苗如何重塑人类血液和鼻黏膜的信息。 可能与预防SARS-CoV-2感染和/或发病率相关的隔间 和COVID的严重程度。

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.