The century-old tuberculosis vaccine BCG has been the focus of renewed interest due to its well-documented ability to protect against various non-TB pathogens. Much of these broad spectrum protective effects are attributed to trained immunity, the epigenetic and metabolic reprogramming of innate immune cells. As BCG vaccine is safe, cheap, widely available, amendable to use as a recombinant vector, and immunogenic, it has immense potential for use as an immunotherapeutic agent for various conditions including autoimmune, allergic, neurodegenerative, and neoplastic diseases as well as a preventive measure against infectious agents. Of particular interest is the use of BCG vaccination to counteract the increasing prevalence of autoimmune and allergic conditions in industrialized countries attributable to reduced infectious burden as described by the ‘hygiene hypothesis.’ Furthermore, BCG vaccination has been proposed as a potential therapy to mitigate spread and disease burden of COVID-19 as a bridge to development of a specific vaccine and recombinant BCG expression vectors may prove useful for the introduction of SARS-CoV-2 antigens (rBCG-SARS-CoV-2) to induce long-term immunity. Understanding the immunomodulatory effects of BCG vaccine in these disease contexts is therefore critical. To that end, we review here BCG-induced immunomodulation focusing specifically on BCG-induced trained immunity and how it relates to the ‘hygiene hypothesis’ and COVID-19.

具有百年历史的结核疫苗卡介苗（BCG）因其有据可查的预防各种非结核病原体的能力而重新成为人们关注的焦点。这些广谱保护作用大部分归因于训练有素的免疫力、先天免疫细胞的表观遗传和代谢重编程。由于卡介苗疫苗安全、廉价、广泛使用、可作为重组载体使用且具有免疫原性，因此它具有作为多种疾病的免疫治疗剂的巨大潜力，包括自身免疫性疾病、过敏性疾病、神经退行性疾病和肿瘤性疾病以及预防性治疗。针对传染源的措施。特别令人感兴趣的是使用卡介苗疫苗接种来抵消工业化国家日益流行的自身免疫和过敏性疾病，这归因于“卫生假说”所描述的感染负担的减少。此外，BCG 疫苗接种已被提议作为减轻 COVID-19 传播和疾病负担的潜在疗法，作为开发特定疫苗的桥梁，而重组 BCG 表达载体可能有助于引入 SARS-CoV-2 抗原 (rBCG) -SARS-CoV-2）诱导长期免疫力。因此，了解卡介苗疫苗在这些疾病中的免疫调节作用至关重要。为此，我们在此回顾 BCG 诱导的免疫调节，特别关注 BCG 诱导的训练免疫及其与“卫生假说”和 COVID-19 的关系。