title: Protective antibody responses against Clostridium difficile elicited by a DNA vaccine expressing the enzymatic domain of toxin B.
abstract: A DNA vaccination approach was used in the current study to screen for the immunogenicity of different fragments of toxin A and toxin B from Clostridium difficile. With this approach, protein antigens do not need to be produced in vitro and the immunogenicity of candidate C. difficile antigens can be identified directly in animals. Codon optimized toxin gene fragments were individually cloned into the DNA vaccine vector and tested in mice and rabbits for their ability to elicit C. difficile toxin-specific antibody responses. Only a subset of the C. difficile toxin fragments, including the C-terminal receptor binding domain of toxin A and a novel N-terminal enzymatic domain of toxin B, were able to elicit protective antibody responses as determined by protection of target cells in a cytotoxicity assay or by preventing death of mice in a passive antibody protection study. Significantly, antibodies elicited by the novel N-terminus of the toxin B DNA vaccine were able to increase the level of protection when used in combination with anti-toxin A antibodies in a toxin challenge model in mice.
authors.affiliation: Jiangsu Province Key Laboratory in Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University; Nanjing, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Jin
authors.forename: Shixia
authors.initials: S
authors.lastname: Wang
authors.forename: Chunhua
authors.initials: C
authors.lastname: Zhang
authors.forename: Yanling
authors.initials: Y
authors.lastname: Xiao
authors.forename: Shan
authors.initials: S
authors.lastname: Lu
authors.forename: Zuhu
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D001427:Bacterial Toxins / Q000235:genetics / Q000276:immunology*; D002470:Cell Survival; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D011041:Poisoning / Q000276:immunology / Q000517:prevention & control; D011817:Rabbits; D016019:Survival Analysis; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile
keywords: Clostridium difficile; DNA vaccine; antibody responses; passive protection; toxin A; toxin B; toxin neutralization