title: Clostridium difficile toxoid vaccine in recurrent C. difficile-associated diarrhea.
abstract: OBJECTIVE
  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-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.
  
  
  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.
authors.affiliation: Gastroenterology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, 02215,USA.
authors.forename: Stavros
authors.initials: S
authors.lastname: Sougioultzis
authors.forename: Lorraine
authors.initials: L
authors.lastname: Kyne
authors.forename: Denise
authors.initials: D
authors.lastname: Drudy
authors.forename: Sarah
authors.initials: S
authors.lastname: Keates
authors.forename: Seema
authors.initials: S
authors.lastname: Maroo
authors.forename: Charalabos
authors.initials: C
authors.lastname: Pothoulakis
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Giannasca
authors.forename: Cynthia K
authors.initials: CK
authors.lastname: Lee
authors.forename: Michel
authors.initials: M
authors.lastname: Warny
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Monath
authors.forename: Ciarán P
authors.initials: CP
authors.lastname: Kelly
mesh_terms: D000328:Adult; D000368:Aged; D000917:Antibody Formation; D001427:Bacterial Toxins / Q000276:immunology; D001428:Bacterial Vaccines / Q000009:adverse effects / Q000627:therapeutic use*; D016360:Clostridioides difficile / Q000276:immunology*; D046508:Culture Techniques; D003967:Diarrhea / Q000382:microbiology* / Q000517:prevention & control*; D004761:Enterocolitis, Pseudomembranous / Q000150:complications* / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D014121:Toxoids / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D014121:Toxoids