Protective efficacy induced by recombinant clostridium difficile toxin fragments

Rosanna Leuzzi, Janice Spencer, Anthony Buckley, Cecilia Brettoni, Manuele Martinelli, Lorenza Tulli, Sara Marchi, Enrico Luzzi, June Irvine, Denise Candlish, Daniele Veggi, Werner Pansegrau, Luigi Fiaschi, Silvana Savino, Erwin Swennen, Osman Cakici, Ernesto Oviedo-Orta, Monica Giraldi, Barbara Baudner, Nunzia D'UrzoDomenico Maione, Marco Soriani, Rino Rappuoli, Mariagrazia Pizza, Gillian R. Douce*, Maria Scarselli*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)

Abstract

Clostridium difficile is a spore-forming bacterium that can reside in animals and humans. C. difficile infection causes a variety of clinical symptoms, ranging from diarrhea to fulminant colitis. Disease is mediated by TcdA and TcdB, two large enterotoxins released by C. difficile during colonization of the gut. In this study, we evaluated the ability of recombinant toxin fragments to induce neutralizing antibodies in mice. The protective efficacies of the most promising candidates were then evaluated in a hamster model of disease. While limited protection was observed with some combinations, coadministration of a cell binding domain fragment of TcdA (TcdA-B1) and the glucosyltransferase moiety of TcdB (TcdB-GT) induced systemic IgGs which neutralized both toxins and protected vaccinated animals from death following challenge with two strains of C. difficile. Further characterization revealed that despite high concentrations of toxin in the gut lumens of vaccinated animals during the acute phase of the disease, pathological damage was minimized. Assessment of gut contents revealed the presence of TcdA and TcdB antibodies, suggesting that systemic vaccination with this pair of recombinant polypeptides can limit the disease caused by toxin production during C. difficile infection.

Original languageEnglish
Pages (from-to)2851-2860
Number of pages10
JournalInfection and Immunity
Volume81
Issue number8
DOIs
Publication statusPublished - Aug 2013

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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