Bovine antibodies targeting primary and recurrent Clostridium difficile disease are a potent antibiotic alternative

Melanie L. Hutton, Bliss A. Cunningham, Kate E. Mackin, Shelley A. Lyon, Meagan L. James, Julian I. Rood, Dena Lyras

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The increased incidence of antibiotic resistant 'superbugs' has amplified the use of broad spectrum antibiotics worldwide. An unintended consequence of antimicrobial treatment is disruption of the gastrointestinal microbiota, resulting in susceptibility to opportunistic pathogens, such as Clostridium difficile. Paradoxically, treatment of C. difficile infections (CDI) also involves antibiotic use, leaving patients susceptible to re-infection. This serious health threat has led to an urgent call for the development of new therapeutics to reduce or replace the use of antibiotics to treat bacterial infections. To address this need, we have developed colostrum-derived antibodies for the prevention and treatment of CDI. Pregnant cows were immunised to generate hyperimmune bovine colostrum (HBC) containing antibodies that target essential C. difficile virulence components, specifically, spores, vegetative cells and toxin B (TcdB). Mouse infection and relapse models were used to compare the capacity of HBC to prevent or treat primary CDI as well as prevent recurrence. Administration of TcdB-specific colostrum alone, or in combination with spore or vegetative cell-targeted colostrum, prevents and treats C. difficile disease in mice and reduces disease recurrence by 67%. C. difficile-specific colostrum should be re-considered as an immunotherapeutic for the prevention or treatment of primary or recurrent CDI.

Original languageEnglish
Article number3665
Number of pages13
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 16 Jun 2017

Keywords

  • antibody therapy
  • bacteriology
  • immunotherapy
  • infection

Cite this

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abstract = "The increased incidence of antibiotic resistant 'superbugs' has amplified the use of broad spectrum antibiotics worldwide. An unintended consequence of antimicrobial treatment is disruption of the gastrointestinal microbiota, resulting in susceptibility to opportunistic pathogens, such as Clostridium difficile. Paradoxically, treatment of C. difficile infections (CDI) also involves antibiotic use, leaving patients susceptible to re-infection. This serious health threat has led to an urgent call for the development of new therapeutics to reduce or replace the use of antibiotics to treat bacterial infections. To address this need, we have developed colostrum-derived antibodies for the prevention and treatment of CDI. Pregnant cows were immunised to generate hyperimmune bovine colostrum (HBC) containing antibodies that target essential C. difficile virulence components, specifically, spores, vegetative cells and toxin B (TcdB). Mouse infection and relapse models were used to compare the capacity of HBC to prevent or treat primary CDI as well as prevent recurrence. Administration of TcdB-specific colostrum alone, or in combination with spore or vegetative cell-targeted colostrum, prevents and treats C. difficile disease in mice and reduces disease recurrence by 67{\%}. C. difficile-specific colostrum should be re-considered as an immunotherapeutic for the prevention or treatment of primary or recurrent CDI.",
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Bovine antibodies targeting primary and recurrent Clostridium difficile disease are a potent antibiotic alternative. / Hutton, Melanie L.; Cunningham, Bliss A.; Mackin, Kate E.; Lyon, Shelley A.; James, Meagan L.; Rood, Julian I.; Lyras, Dena.

In: Scientific Reports, Vol. 7, No. 1, 3665, 16.06.2017.

Research output: Contribution to journalArticleResearchpeer-review

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