title: A DNA vaccine targeting TcdA and TcdB induces protective immunity against Clostridium difficile.
abstract: BACKGROUND
  Clostridium difficile-associated disease (CDAD) constitutes a great majority of hospital diarrhea cases in industrialized countries and is induced by two types of large toxin molecules: toxin A (TcdA) and toxin B (TcdB). Development of immunotherapeutic approaches, either active or passive, has seen a resurgence in recent years. Studies have described vaccine plasmids that express either TcdA and/or TcdB receptor binding domain (RBD). However, the effectiveness of one vector encoding both toxin RBDs against CDAD has not been evaluated.
  
  
  METHODS
  In the study, we constructed highly optimized plasmids to express the receptor binding domains of both TcdA and TcdB from a single vector. The DNA vaccine was evaluated in two animal models for its immunogenicity and protective effects.
  
  
  RESULTS
  The DNA vaccine induced high levels of serum antibodies to toxin A and/or B and demonstrated neutralizing activity in both in vitro and in vivo systems. In a C. difficile hamster infection model, immunization with the DNA vaccine reduced infection severity and conferred significant protection against a lethal C. difficile strain.
  
  
  CONCLUSIONS
  This study has demonstrated a single plasmid encoding the RBD domains of C. difficile TcdA and TcdB as a DNA vaccine that could provide protection from C. difficile disease.
authors: School of Biomedical Sciences, The University of Hong Kong, Li Ka Shing Faculty of Medicine, 3/F, Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong, China.|Department of Microbiology, The University of Hong Kong, University Pathology Building, Pokfulam, Hong Kong, China.|HKU-Shenzhen Institute of Research and Innovation, The University of Hong Kong, Shenzhen, China.
authors: Bao-Zhong
authors: BZ
authors: Zhang
authors: Department of Microbiology, The University of Hong Kong, University Pathology Building, Pokfulam, Hong Kong, China.
authors: Jianpiao
authors: J
authors: Cai
authors: School of Biomedical Sciences, The University of Hong Kong, Li Ka Shing Faculty of Medicine, 3/F, Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong, China.
authors: Bin
authors: B
authors: Yu
authors: School of Biomedical Sciences, The University of Hong Kong, Li Ka Shing Faculty of Medicine, 3/F, Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong, China.
authors: Yanhong
authors: Y
authors: Hua
authors: Department of Microbiology, The University of Hong Kong, University Pathology Building, Pokfulam, Hong Kong, China.
authors: Candy Choiyi
authors: CC
authors: Lau
authors: Department of Microbiology, The University of Hong Kong, University Pathology Building, Pokfulam, Hong Kong, China.
authors: Richard Yi-Tsun Tsun
authors: RY
authors: Kao
authors: Department of Microbiology, The University of Hong Kong, University Pathology Building, Pokfulam, Hong Kong, China.
authors: Kong-Hung
authors: KH
authors: Sze
authors: Department of Microbiology, The University of Hong Kong, University Pathology Building, Pokfulam, Hong Kong, China. kyyuen@hkucc.hku.hk.
authors: Kwok-Yung
authors: KY
authors: Yuen
authors: School of Biomedical Sciences, The University of Hong Kong, Li Ka Shing Faculty of Medicine, 3/F, Laboratory Block, 21 Sassoon Road, Pokfulam, Hong Kong, China. jdhuang@hku.hk.|HKU-Shenzhen Institute of Research and Innovation, The University of Hong Kong, Shenzhen, China. jdhuang@hku.hk.|The Centre for Synthetic Biology Engineering Research, Shenzhen Institutes of Advanced Technology, Chinese Academy of Science, Shenzhen, China. jdhuang@hku.hk.
authors: Jian-Dong
authors: JD
authors: Huang
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D001427:Bacterial Toxins / Q000235:genetics*; D001428:Bacterial Vaccines / Q000235:genetics / Q000276:immunology*; D019556:COS Cells; D016360:Clostridioides difficile / Q000235:genetics / Q000472:pathogenicity*; D004761:Enterocolitis, Pseudomembranous / Q000276:immunology / Q000517:prevention & control; D004768:Enterotoxins / Q000235:genetics*; D005260:Female; D008647:Mesocricetus; D008807:Mice, Inbred BALB C; D010957:Plasmids; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D004768:Enterotoxins; D019444:Vaccines, DNA; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile
keywords: Clostridium difficile; DNA vaccine; Toxin A (TcdA); Toxin B (TcdB)