BCG, muramylpeptides, trained immunity (part II): a low molecular weight alternative to multicomponent bacterial immunostimulants for prevention of respiratory infections during a pandemic

Abstract

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.

Uncovering the genetic links of SARS‐CoV‐2 infections on heart failure co‐morbidity by a systems biology approach

“…The microbe‐derived immunostimulatory agents have gained popularity against SARS‐CoV‐2. Particularly, as promising pharmaceutical substances, MDPs can reproduce the nonspecific effects of multicomponent bacterial adjuvants, immunostimulants, and vaccines in preventing risk factors during the pandemic 87 …”

“…Particularly, as promising pharmaceutical substances, MDPs can reproduce the nonspecific effects of multicomponent bacterial adjuvants, immunostimulants, and vaccines in preventing risk factors during the pandemic. 87 Adequate GSH level is critical for antiviral defence and immune system protection through the anti-oxidant mechanism. 88 Endogenous GSH deficiency exacerbates SARS-CoV-2-induced oxidative damage and uncontrolled SARS-CoV-2 reproduction, leading to excessive inflammatory response and further multiple organ failure.…”

Adjuvant effects of multifunctional transcription factor and BCG target YB-1: exogenous YB-1 enhances specific antibody productionin vivoand protects mice against lethalE. colichallenge

“…Further experiments will be necessary to determine whether administration of YB-1, independently of or in conjunction with its ligands GMDP/MDP, can influence cytokine secretion and offer significant protection not only against acute infections of outstanding topical interest (i.e., COVID [66]) but also against protracted infections such as those implicated in neurodegenerative diseases including AD and multiple sclerosis.…”