Clostridium difficile toxoid vaccine in recurrent C. difficile-associated diarrhea

Gastroenterology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, 02215,USA.
Gastroenterology (Impact Factor: 16.72). 03/2005; 128(3):764-70. DOI: 10.1053/j.gastro.2004.11.004
Source: PubMed


Recurrent C difficile -associated diarrhea (CDAD) is associated with a lack of protective immunity to C difficile toxins. A parenteral C difficile vaccine containing toxoid A and toxoid B was reported previously to be safe and immunogenic in healthy volunteers. Our aim was to examine whether the vaccine is also well tolerated and immunogenic in patients with recurrent CDAD.
Subjects received 4, 50-microg intramuscular inoculations of the C difficile vaccine over an 8-week period. Serum antitoxin antibodies were measured by ELISA, and toxin neutralizing activity was evaluated using the tissue culture cytotoxin assay.
Three patients with multiple episodes of recurrent CDAD were vaccinated. Two of the 3 showed an increase in serum IgG antitoxin A antibodies (3-fold and 4-fold increases, respectively) and in serum IgG antitoxin B antibodies (52-fold and 20-fold, respectively). Both also developed cytotoxin neutralizing activity against toxin A and toxin B. Prior to vaccination, the subjects had required nearly continuous treatment with oral vancomycin for 7, 9, and 22 months, respectively, to treat recurrent episodes of CDAD. After vaccination, all 3 subjects discontinued treatment with oral vancomycin without any further recurrence.
A C difficile toxoid vaccine induced immune responses to toxins A and B in patients with CDAD and was associated with resolution of recurrent diarrhea. The results of this study support the feasibility of active vaccination against C difficile and its toxins in high-risk individuals but must be validated in larger, randomized, controlled trials.

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    • "One of the approaches to prevention of C. difficile infection is the development of an effective vaccine. Toxoids A and B are the best candidates for C. difficile vaccine and they are able to exert excellent serum antibody responses in healthy adults [54]. As a first report of a DNA vaccine targeting C. difficile toxins, Gardiner et al. explained the receptor-binding domain of C. difficile toxin A that is able to induce well immune responses in mice and protect them from death. "
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    • "A vaccine based on formaldehyde-inactivated TcdA and TcdB has been developed and used in healthy volunteers, and induced high levels of specific neutralizing IgG. Initial studies have been conducted with promising results in a few patients with recurrent CDI [6]. "
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    • "Furthermore, reduction in recurrence of CDAD was achieved in a Phase I clinical trial with A and B toxin monoclonal antibodies in combination with standard antibiotic therapy (Lowy et al., 2010). In addition, in a small study with three patients with chronic relapsing CDAD, an investigational vaccine using formalininactivated A and B toxoid antigens prevented CDAD recurrence (Sougioultzis et al., 2005). Collectively, these observations provide validation for, and encourage further development of C. difficile toxin A-and B-based vaccines to prevent CDAD. "
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