title: Antibody against TcdB, but not TcdA, prevents development of gastrointestinal and systemic Clostridium difficile disease.
abstract: BACKGROUND
  A dramatic increase in morbidity and mortality from Clostridium difficile infection (CDI) due to the recent emergence of virulent, antibiotic-resistant strains has led to a search for alternatives to antibiotics, including vaccines and immune-based therapy that target the 2 key toxins-TcdA and TcdB.
  
  
  METHODS
  We investigated the efficacy of specific human monoclonal antibodies (HuMab) and alpaca polyclonal antibodies against each toxin separately and in combination in the gnotobiotic piglet model of CDI. Additionally, the HuMab and polyclonal antibodies were exploited to investigate the precise contribution of each toxin to systemic and/or gastrointestinal (GI) tract disease.
  
  
  RESULTS
  Our results indicate that TcdB is an important virulence factor associated with GI and systemic pathology. Administration of anti-TcdB antibody alone or with anti-TcdA protected 100% of piglets from development of systemic CDI and minimized GI lesions. Conversely, 100% of piglets administered only anti-TcdA developed severe GI and systemic disease, with 67%-83% fatality, faring worse than placebo-treated control animals.
  
  
  CONCLUSIONS
  These results highlight the importance of TcdB in the pathogenesis of CDI and the effectiveness of TcdB-specific antibody in treating CDI. However, the results raise new questions regarding the nature of TcdA interaction with therapeutic antibodies.
authors.affiliation: Tufts Cummings School of Veterinary Medicine, Department of Biomedical Sciences, Division of Infectious Diseases, North Grafton, MA 01536, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Steele
authors.forename: Jean
authors.initials: J
authors.lastname: Mukherjee
authors.forename: Nicola
authors.initials: N
authors.lastname: Parry
authors.forename: Saul
authors.initials: S
authors.lastname: Tzipori
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology*; D016360:Clostridioides difficile / Q000276:immunology / Q000472:pathogenicity*; D003015:Clostridium Infections / Q000276:immunology / Q000517:prevention & control*; D004761:Enterocolitis, Pseudomembranous / Q000276:immunology* / Q000517:prevention & control*; D004768:Enterotoxins / Q000276:immunology*; D041981:Gastrointestinal Tract / Q000276:immunology / Q000473:pathology; D005856:Germ-Free Life; D006801:Humans; D013552:Swine
chemical_list: D000907:Antibodies, Bacterial; D061067:Antibodies, Monoclonal, Humanized; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile