Clostridium difficile toxoid vaccine in recurrent C. difficile-associated diarrhea
Autor: | Sarah Keates, Paul J. Giannasca, Ciaran P. Kelly, Charalabos Pothoulakis, Cynthia K. Lee, Lorraine Kyne, Seema Maroo, Michel Warny, D. Drudy, Thomas P. Monath, Stavros Sougioultzis |
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Rok vydání: | 2005 |
Předmět: |
Adult
Diarrhea Male Bacterial Toxins Clostridium difficile toxin A Recurrence Culture Techniques medicine Humans Enterocolitis Pseudomembranous Aged Enterocolitis Hepatology biology Clostridioides difficile business.industry Gastroenterology Toxoid Middle Aged Toxoids Clostridium difficile Vaccination Antibody Formation Bacterial Vaccines Immunology biology.protein Female medicine.symptom Antibody Antitoxin business |
Zdroj: | Gastroenterology. 128:764-770 |
ISSN: | 0016-5085 |
Popis: | Background & aims: 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. Methods: Subjects received 4, 50-μg 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. Results: 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. Conclusions: 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. |
Databáze: | OpenAIRE |
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