Adjuvant effects of multifunctional transcription factor and BCG ‎target YB-1: exogenous YB-1 enhances specific antibody ‎production in vivo and protects mice against lethal E. coli ‎challenge

There is growing interest in the beneficial effects of immune system boosting through the administration of adjuvants, not only in acute infections such as COVID but also in chronic degenerative disorders that are potentially associated with infection. The best-known immunopotentiators are Freunds complete adjuvant (FCA) and its relative Bacille Calmete-Guerin (BCG), both based on Mycobacterium species. The key pathogen-associated molecular patterns (PAMPs) in both FCA and BCG are muramyl dipeptides (MDPs and glucosaminyl-MDP, GMDP). We previously identified the evolutionarily conserved protein Y-box factor YB-1/YBX1 as a primary target for MDP/GMDP. Unlike other host receptors for PAMPs, YB-1 is a diffusible molecule, and we therefore explored whether in vivo administration of YB-1, rather than its PAMP ligands, might enhance the immune response to a bacterial antigen and/or influence survival in the face of bacterial infection. We report that mice receiving YB-1 plus GMDP in vivo mount a significantly increased B cell response versus GMDP alone against a test antigen (Yersinia pestis V antigen), and that YB-1 administration alone significantly promotes survival in the face of lethal bacterial (Escherichia coli) challenge in vivo. Independent confirmation is warranted because recombinant YB-1 and its ligands could hold great promise both as adjuvants and as therapeutics.