Abstract
The receptor-binding domains (RBDs) located in toxin A and toxin B of Clostridium difficile are known to be nontoxic and immunogenic. We need to develop a new type vaccine based on RBDs. In this study, we expressed and purified recombinant proteins (named RBD-TcdA and RBD-TcdB) as vaccine candidates containing the RBDs of toxin A and toxin B, respectively, from the C. difficile reference strain VPI10463. The immunogenicity and protection of the vaccine candidates RBD-TcdA, RBD-TcdB, and RBD-TcdA/B was evaluated by ELISA and survival assays. The data indicated that mice immunized with all vaccine candidates displayed potent levels of RBD-specific serum IgG. Following intramuscular immunization of mice with RBD-TcdA and/or RBD-TcdB, these vaccine candidates triggered immune responses that protected mice compared to mice immunized with aluminum hydroxide alone. Taken together, the results of this study reveal that recombinant proteins containing RBDs of C. difficile toxins can be used for vaccine development. Additionally, we found that an RBD-TcdA/B vaccine can elicit a stronger humoral immune response and provide better immunoprotection than the univalent vaccines. This RBD vaccine candidate conferred significant protection against disease symptoms and death caused by toxins from a wild-type C. difficile strain.
Highlights
Clostridium difficile or Clostridiodes difficile [1] is a gram-positive, spore-forming, anaerobic rod bacterium that barely received attention before it was discovered to be associated with pseudomembranous colitis in 1978 [2,3]
Fragments encoding the C-terminal receptor-binding domains (RBDs) of toxin A or toxin B were generated to produce recombinant
There has been an increase in the occurrence of C. difficile infection (CDI), which is related to certain risk factors, especially the use of antibiotics
Summary
Clostridium difficile or Clostridiodes difficile [1] is a gram-positive, spore-forming, anaerobic rod bacterium that barely received attention before it was discovered to be associated with pseudomembranous colitis in 1978 [2,3] It causes more than 25% of the cases of antibiotic-associated diarrhea [1,2]. Most CDIs are caused by a new strain belonging to ribotype 027 (RT027), which spread worldwide in 2003 and resulted in a large number of deaths [6,7]. It has been on the legal surveillance list in many countries, including China, as a pathogen causing infectious disease [8,9]. Besides the use of effective antibiotics and fecal microbiota transplantation (FMT), immunoprophylaxis is generally considered an effective and preferred control strategy [10,11]
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