Kalyuzhin O V, Andronova T M, Karaulov A V
Sechenov First Moscow State Medical University (Sechenov University).
Peptek.
Ter Arkh. 2021 Jan 10;93(1):108-113. doi: 10.26442/00403660.2021.01.200554.
During a pandemic, nonspecific immunoprophylaxis of SARS-CoV-2 infection and other acute respiratory infections (ARI), which can worsen the course of COVID-19, is increasingly in demand in addition to specific immunization. BCG vaccine appears to be one of the candidate immunostimulants in this regard. At the same time, other microbe-derived preparations capable of inducing a state of trained immunity deserve attention. BCG and other bacterial immunostimulatory agents containing a large number of biologically active subunits have long been considered as objects of search for promising pharmacological substances. The review analyzes the linkages between BCG, mycobacterial adjuvants, bacterial lysates, trained immunity, muramylpeptides (MPs) and NOD2 receptors in light of the choice of a low molecular weight alternative to multicomponent bacterial immunostimulants for ARI prevention during the COVID-19 pandemic. The search for key molecules by which bacteria stimulate innate and adaptive immune responses proceeds in a spiral. On different loops of this spiral, MPs have repeatedly reproduced the nonspecific effects of multicomponent bacterial adjuvants, vaccines and immunostimulants. MPs and peptidoglycans containing MPs determine the adjuvant properties of the cell walls of mycobacteria and their peptide-glycolipid fraction (wax D). MPs were able to replace Mycobacterium tuberculosis in complete Freunds adjuvant. MPs determine the NOD2-dependent ability of BCG to induce trained immunity. Probably, MPs provide NOD2-mediated long-term prophylactic action of bacterial lysates. All of the above has prompted revisiting the previously obtained evidence of the efficacy of glucosaminylmuramyl dipeptide (GMDP) as a NOD2 agonist in treatment/prevention of respiratory infections. We speculate here that MPs, in particular GMDP, at rational dosing regimens will be able to reproduce many aspects of the nonspecific effects of BCG and multicomponent bacterial immunostimulants in preventing ARI during the COVID-19 pandemic and in the post-pandemic period.
在大流行期间，除了特异性免疫接种外，对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染以及可能使新型冠状病毒肺炎（COVID-19）病情恶化的其他急性呼吸道感染（ARI）进行非特异性免疫预防的需求日益增加。卡介苗似乎是这方面的候选免疫刺激剂之一。与此同时，其他能够诱导训练有素的免疫状态的微生物衍生制剂也值得关注。卡介苗和其他含有大量生物活性亚基的细菌免疫刺激剂长期以来一直被视为寻找有前景的药理物质的对象。本综述根据在COVID-19大流行期间预防ARI时选择低分子量的多组分细菌免疫刺激剂替代品的情况，分析了卡介苗、分枝杆菌佐剂、细菌裂解物、训练有素的免疫、胞壁酰肽（MPs）和NOD2受体之间的联系。对细菌刺激先天性和适应性免疫反应的关键分子的探索呈螺旋式进行。在这个螺旋的不同环节上，MPs反复重现了多组分细菌佐剂、疫苗和免疫刺激剂的非特异性作用。含有MPs的MPs和肽聚糖决定了分枝杆菌细胞壁及其肽糖脂部分（蜡质D）的佐剂特性。MPs能够替代完全弗氏佐剂中的结核分枝杆菌。MPs决定了卡介苗诱导训练有素的免疫的NOD2依赖性能力。可能，MPs提供了细菌裂解物的NOD2介导的长期预防作用。上述所有情况促使人们重新审视先前获得的关于葡糖胺酰胞壁酰二肽（GMDP）作为NOD2激动剂在治疗/预防呼吸道感染方面疗效的证据。我们在此推测，在合理的给药方案下，MPs，特别是GMDP，将能够重现卡介苗和多组分细菌免疫刺激剂在预防COVID-19大流行期间和大流行后时期的ARI方面的许多非特异性作用。
