title: Serum anti-toxin B antibody correlates with protection from recurrent Clostridium difficile infection (CDI).
abstract: BACKGROUND
  Previous studies have demonstrated a correlation between Clostridium difficile anti-toxin A serum antibodies and protection against symptomatic disease and recurrence.
  
  
  METHODS
  A neutralizing monoclonal antibody to C. difficile toxin A (CDA1) developed by MBL and Medarex, Inc. was studied in a phase II, randomized, double-blind, placebo-controlled trial in patients receiving standard of care treatment for C. difficile infection (CDI). Twenty-nine subjects received a single intravenous infusion of 10mg/kg CDA1 and 17 subjects received placebo and were evaluated for recurrence of CDI during the 56-day study period. Serum antibodies against C. difficile toxin A and B were measured by ELISA and cytotoxicity assay at various time points before and after infusion.
  
  
  RESULTS
  CDI recurrence occurred in 5 of 29 (17%) in the CDA1 group and 3 of 17 (18%) (p=NS) in the placebo group with a trend toward delay in time to recurrence in the group treated with CDA1. The geometric mean concentration of antibody to an epitope of the receptor-binding domain of toxin B (0.300 and 1.20microg/ml, respectively; p=0.02) and geometric mean titer of neutralizing B antibody (8.00 and 100, respectively; p=0.02) at study day 28 were lower for those subjects with recurrence compared to those who did not recur. In addition, a significantly greater proportion of subjects who recurred were infected with the epidemic BI/NAP1/027 strain compared with those that did not recur (88% vs. 22%; p=0.002). Finally, in a multiple logistic regression analysis neutralizing anti-toxin B at day 14 (p<0.001), anti-toxin A at day 28 (p<0.001) and infection with the BI/NAP1/027 strain at enrollment (p=0.002) were all predictive of CDI recurrence.
  
  
  CONCLUSIONS
  In this prospective study, lower concentrations of neutralizing anti-toxin B and anti-toxin A antibody and infection with the BI/NAP1/027 strain of C. difficile were significantly associated with recurrence of CDI.
authors: MassBiologics, University of Massachusetts Medical School, Boston, MA, USA. brett.leav@umassmed.edu
authors: Brett A
authors: BA
authors: Leav
authors: Barbra
authors: B
authors: Blair
authors: Mark
authors: M
authors: Leney
authors: Michael
authors: M
authors: Knauber
authors: Courtney
authors: C
authors: Reilly
authors: Israel
authors: I
authors: Lowy
authors: Dale N
authors: DN
authors: Gerding
authors: Ciarán P
authors: CP
authors: Kelly
authors: Kia
authors: K
authors: Katchar
authors: Roger
authors: R
authors: Baxter
authors: Donna
authors: D
authors: Ambrosino
authors: Deborah
authors: D
authors: Molrine
mesh_terms: D000368:Aged; D000907:Antibodies, Bacterial / Q000008:administration & dosage / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000097:blood*; D000992:Antitoxins / Q000008:administration & dosage / Q000097:blood*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D004311:Double-Blind Method; D004761:Enterocolitis, Pseudomembranous / Q000276:immunology / Q000517:prevention & control*; D004768:Enterotoxins / Q000037:antagonists & inhibitors* / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D010919:Placebos / Q000008:administration & dosage; D011446:Prospective Studies; D055502:Secondary Prevention
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D000992:Antitoxins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D015415:Biomarkers; D004768:Enterotoxins; D010919:Placebos; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile