Kalyuzhin O V, Andronova T M, Karaulov A V
Sechenov First Moscow State Medical University (Sechenov University).
Peptek.
Ter Arkh. 2020 Dec 15;92(12):195-200. doi: 10.26442/00403660.2020.12.200464.
It has long been known that Bacillus CalmetteGurin (BCG) vaccine provides nonspecific protection against many non-mycobacterial infections, which has been discussed in the last decade through the prism of the concept of trained immunity. Within the framework of this concept, a persistent increase in resistance to various pathogens, which occurs after an infectious disease or exposure to certain microbial agents, is associated with epigenetic reprogramming of innate immune cells and their bone marrow progenitors. The COVID-19 pandemic has drawn attention of scientists and practitioners to BCG as an inducer of trained immunity. A number of epidemiological studies have suggested a negative association between the coverage of the population with BCG vaccination and the burden of SARS-CoV-2 infection. A series of independent clinical studies of the effectiveness of this vaccine in non-specific prevention of COVID-19 has been initiated in different countries. Recently, the key role of cytosolic NOD2 receptors in BCG-induced trained immunity has been proven. This actualizes the search for effective immunoactive preparations for prevention of respiratory infections in the pandemic among low molecular weight peptidoglycan fragments of the bacterial cell wall, muramylpeptides (MPs), which are known to be NOD2 agonists. The review highlights the proven and proposed linkages between BCG, MPs, NOD2 and trained immunity in the light of the COVID-19 pandemic. Analysis of the data presented indicates the prospects for preclinical and clinical studies of MPs as potential drugs for nonspecific prevention of SARS-CoV-2 infection and/or other respiratory infections in risk groups during the pandemic. First of all, attention should be paid to glucosaminylmuramyl dipeptide, approved for clinical use in Russia and a number of post-Soviet countries for the complex treatment and prevention of acute and recurrent respiratory infections.
长期以来，人们一直知道卡介苗（BCG）疫苗能为许多非分枝杆菌感染提供非特异性保护，在过去十年中，通过训练免疫的概念对此进行了讨论。在这一概念的框架内，传染病或接触某些微生物制剂后对各种病原体的抵抗力持续增强，这与先天免疫细胞及其骨髓祖细胞的表观遗传重编程有关。新冠疫情使科学家和从业者将注意力转向卡介苗作为训练免疫的诱导剂。一些流行病学研究表明，人群中卡介苗接种覆盖率与新冠病毒感染负担之间存在负相关。不同国家已启动了一系列关于该疫苗非特异性预防新冠的有效性的独立临床研究。最近，已证实胞质NOD2受体在卡介苗诱导的训练免疫中起关键作用。这使得在细菌细胞壁的低分子量肽聚糖片段——胞壁酰肽（MPs）中寻找预防大流行期间呼吸道感染的有效免疫活性制剂成为当务之急，已知MPs是NOD2激动剂。鉴于新冠疫情，本综述强调了已证实的以及提出的卡介苗、MPs、NOD2与训练免疫之间的联系。对所呈现数据的分析表明，MPs作为大流行期间非特异性预防新冠病毒感染和/或其他呼吸道感染的潜在药物，在临床前和临床研究方面具有前景。首先，应关注氨基葡糖胞壁酰二肽，它在俄罗斯和一些前苏联国家已被批准用于急性和复发性呼吸道感染的综合治疗和预防。
