title: A chimeric protein comprising the glucosyltransferase and cysteine proteinase domains of toxin B and the receptor binding domain of toxin A induces protective immunity against Clostridium difficile infection in mice and hamsters.
abstract: Clostridium difficile is the major cause of hospital-acquired infectious diarrhea and colitis in developed countries. The pathogenicity of C. difficile is mainly mediated by the release of 2 large potent exotoxins, toxin A (TcdA) and toxin B (TcdB), both of which require neutralization to prevent disease occurrence. We have generated a novel chimeric protein, designated mTcd138, comprised of the glucosyltransferase and cysteine proteinase domains of TcdB and the receptor binding domain of TcdA and expressed it in Bacillus megaterium. To ensure that mTcd138 is atoxic, 2 point mutations were introduced to the glucosyltransferase domain of TcdB, which essentially eliminates toxicity of mTcd138. Parenteral immunizations of mice and hamsters with mTcd138 induced protective antibodies to both toxins and provided protection against infection with the hyper-virulent C. difficile strain UK6.
authors.affiliation: a Department of Infectious Diseases and Global Health ; Tufts University Cummings School of Veterinary Medicine ; North Grafton , MA USA.
authors.forename: Yuan-Kai
authors.initials: YK
authors.lastname: Wang
authors.forename: Ya-Xian
authors.initials: YX
authors.lastname: Yan
authors.forename: Hyeun Bum
authors.initials: HB
authors.lastname: Kim
authors.forename: Xianghong
authors.initials: X
authors.lastname: Ju
authors.forename: Song
authors.initials: S
authors.lastname: Zhao
authors.forename: Keshan
authors.initials: K
authors.lastname: Zhang
authors.forename: Saul
authors.initials: S
authors.lastname: Tzipori
authors.forename: Xingmin
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001410:Bacillus megaterium / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D016360:Clostridioides difficile / Q000276:immunology*; D003015:Clostridium Infections / Q000276:immunology / Q000517:prevention & control*; D057056:Cysteine Proteases / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000235:genetics / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D005964:Glucosyltransferases / Q000235:genetics / Q000276:immunology; D008647:Mesocricetus; D008810:Mice, Inbred C57BL; D050505:Mutant Proteins / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D016896:Treatment Outcome; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D004768:Enterotoxins; D050505:Mutant Proteins; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile; D005964:Glucosyltransferases; D057056:Cysteine Proteases
keywords: Clostridium difficile infection; chimeric protein; vaccine