BCG, muramylpeptides, trained immunity (part I): linkages in the light of the COVID-19 pandemic

Abstract

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.

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

“…In sum, our findings demonstrate that exogenous administration of a host immunomodulatory transcription factor, YB-1, can boost in vivo B cell responses; moreover, short (12 h) pre-exposure to YB-1 was found to protect against acute lethal challenge with E. coli. 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.…”

Bacillus Calmette-Guérin–induced trained immunity protects against SARS-CoV-2 challenge in K18-hACE2 mice

“…More recent studies revealed that BCG immunization provides significant protection against viral infections by inducing trained immunity (28)(29)(30). In this direction, the potential benefits of BCG vaccination on protecting against COVID-19 have been actively postulated (18,20,(31)(32)(33)(34)(35)(36)(37). Martha et.…”