Vaccine Targeting TNF Epitope 1-14 Do Not Suppress Host Defense Against Mycobacterium Bovis Bacillus Calmette-Guérin Infection.

Anti-TNF inhibitors are efficacious in the treatment of chronic inflammatory diseases such as rheumatoid arthritis (RA), Crohn's disease (CD), juvenile idiopathic arthritis (JIA), and ankylosing spondylitis (AS). However, more andmore clinical case reports revealed that anti-TNF inhibitors could increase the risk of viral, fungal, and bacterial (especially intracellular) infection. In this study, based on Immune Epitope Database (IEDB) online B cell epitope prediction and the knowledge of TNF three dimensional (3D) structure we developed a novel vaccine (DTNF114-TNF114) that targeting TNF epitope 1-14, which produced antibodies only partially binding to trans-membrane TNF (tmTNF), therefore partially sparing tmTNF-TNFR1/2 interaction. Immunization with DTNF114-TNF114 significantly protected and prolonged the survival rate of mice challenged with lipopolysaccharide (LPS); and in themCherry expressing Mycobacterium bovis Bacillus Calmette-Guerin (mCherry-BCG) infection model, DTNF114-TNF114 immunization significantly decreased soluble TNF (solTNF) level in serum, meanwhile did not suppress host immunity against infection. Thus, this novel and infection concern-free vaccine provides a potential alternative or supplement to currently clinically used anti-TNF inhibitors. (C) 2020 Elsevier B.V. All rights reserved.