Serum Anti-Toxin B Antibody Correlates With Protection From Recurrent Clostridium Difficile Infection (CDI)

Vaccine. 2010 Jan 22;28(4):965-9. doi: 10.1016/j.vaccine.2009.10.144. Epub 2009 Nov 24.

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.

Findings: 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.

Interpretation: 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.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Bacterial / administration & dosage
  • Antibodies, Bacterial / blood*
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / blood*
  • Antitoxins / administration & dosage
  • Antitoxins / blood*
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / immunology
  • Bacterial Toxins / antagonists & inhibitors*
  • Bacterial Toxins / immunology
  • Biomarkers / blood
  • Double-Blind Method
  • Enterocolitis, Pseudomembranous / immunology
  • Enterocolitis, Pseudomembranous / prevention & control*
  • Enterotoxins / antagonists & inhibitors*
  • Enterotoxins / immunology
  • Female
  • Humans
  • Male
  • Placebos / administration & dosage
  • Prospective Studies
  • Secondary Prevention

Substances

  • Antibodies, Bacterial
  • Antibodies, Monoclonal
  • Antitoxins
  • Bacterial Proteins
  • Bacterial Toxins
  • Biomarkers
  • Enterotoxins
  • Placebos
  • tcdA protein, Clostridium difficile
  • toxB protein, Clostridium difficile