anti-TcdB (Clostridioides difficile exotoxin), mAb (rec.) (VIF090-A6)

Clostridioides difficile is a spore-forming, anaerobic, and gram-positive bacterium, that opportunistically colonizes human colon and induces diseases such as diarrhea and pseudomembranous colitis. The symptoms of C. difficile infection (CDI) are mainly caused by two primary exotoxins, TcdA and TcdB, released from the bacterium. Both TcdA and TcdB belong to the family of large clostridial toxins (LCTs), which contain an N-terminal glucosyltransferase domain that modifies small GTPase proteins, a cysteine protease domain (CPD) that autocatalytically cleave the holotoxin in the cytosol, a combined domain for both delivery and receptor binding, and a C-terminal region consisting of series of combined repetitive oligopeptides (CROPs). These toxins enter host cells via receptor-mediated endocytosis and inactivate small GTPase proteins, leading to actin cytoskeleton disruption and cell death. Of the two toxins, TcdB alone is able to induce a full spectrum of diseases in both animals and humans. Although different toxin receptors have been identified, it is no valid therapeutic option to prevent receptor endocytosis. Neutralizing antibodies, directly targeting both toxins are so far the only therapeutic approaches.