Serum anti-toxin B antibody correlates with protection from recurrent Clostridium difficile infection (CDI)

Brett A. Leav, Barbra Blair, Mark Leney, Michael Knauber, Courtney Reilly, Israel Lowy, Dale N. Gerding, Ciarán P. Kelly, Kia Katchar, Roger Baxter, Donna Ambrosino, Deborah Molrine

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187 Scopus citations

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 10 mg/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 1.20 μg/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.

Original languageEnglish
Pages (from-to)965-969
Number of pages5
JournalVaccine
Volume28
Issue number4
DOIs
StatePublished - 22 Jan 2010
Externally publishedYes

Keywords

  • Clostridium difficile
  • Monoclonal antibody
  • Toxin

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