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Toxins (Basel). 2019 Feb 6;11(2). pii: E98. doi: 10.3390/toxins11020098.

Treatment and Prevention of Recurrent Clostridium difficile Infection with Functionalized Bovine Antibody-Enriched Whey in a Hamster Primary Infection Model.

Author information

1
Chair of Food and Bioprocess Engineering, Technical University of Munich, 85354 Freising, Germany. Hans-Juergen.Heidebrecht@tum.de.
2
ZIEL Institute for Food & Health, Technical University of Munich, 85354 Freising, Germany. Hans-Juergen.Heidebrecht@tum.de.
3
University of North Texas Health Science Center, Fort Worth, TX 76107-2699, USA. William.Weiss@unthsc.edu.
4
University of North Texas Health Science Center, Fort Worth, TX 76107-2699, USA. Mark.Pulse@unthsc.edu.
5
tgcBIOMICS GmbH, 55411 Bingen, Germany. a.lange@tgcbiomics.de.
6
tgcBIOMICS GmbH, 55411 Bingen, Germany. k.gisch@tgcbiomics.de.
7
Chair of Animal Physiology and Immunology, Technical University of Munich, 85354 Freising, Germany. kliem@wzw.tum.de.
8
Biosys UK Limited, London, SW1H, 9BP, UK. sacha.mann@gmail.com.
9
Chair of Animal Physiology and Immunology, Technical University of Munich, 85354 Freising, Germany. michael.pfaffl@wzw.tum.de.
10
School of Life Science, Technical University of Munich, 85354 Freising, Germany. michael.pfaffl@wzw.tum.de.
11
Chair of Food and Bioprocess Engineering, Technical University of Munich, 85354 Freising, Germany. ulrich.kulozik@tum.de.
12
ZIEL Institute for Food & Health, Technical University of Munich, 85354 Freising, Germany. ulrich.kulozik@tum.de.
13
tgcBIOMICS GmbH, 55411 Bingen, Germany. chv.eichel@tgcbiomics.de.

Abstract

Toxin-induced Clostridium difficile infection (CDI) is a major disease characterized by severe diarrhea and high morbidity rates. The aim with this study was to develop an alternative drug for the treatment of CDI. Cows were repeatedly immunized to establish specific immunoglobulin G and A titers against toxins A (TcdA) and B (TcdB) and against C. difficile cells in mature milk or colostrum. The effect of three different concentrations of anti-C. difficile whey protein isolates (anti-CD-WPI) and the standard of care antibiotic vancomycin were investigated in an animal model of CD infected hamsters (6 groups, with 10 hamsters each). WPI obtained from the milk of exactly the same cows pre-immunization and a vehicle group served as negative controls. The survival of hamsters receiving anti-CD-WPI was 50, 80 and 100% compared to 10 and 0% for the control groups, respectively. Vancomycin suppressed the growth of C. difficile and thus protected the hamsters at the time of administration, but 90% of these hamsters nevertheless died shortly after discontinuation of treatment. In contrast, the surviving hamsters of the anti-CD-WPI groups survived the entire study period, although they were treated for only 75 h. The specific antibodies not only inactivated the toxins for initial suppression of CDI, but also provoked the inhibition of C. difficile growth after discontinuation, thus preventing recurrence. Oral administration of anti-CD-WPI is a functional therapy of CDI in infected hamsters for both primary treatment and prevention of recurrence. Thus, anti-CD-WPI could address the urgent unmet medical need for treating and preventing recurrent CDI in humans.

KEYWORDS:

Clostridium difficile infection; bovine milk; hamster model of CDI; prevention of recurrence; sIgA

PMID:
30736358
DOI:
10.3390/toxins11020098
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Conflict of interest statement

C.V.E.-S. has received research grants from Biosys UK Limited. S.M. has served as an employee for Biosys UK Limited received personal fees during and outside the study. H.-J.H., W.J.W., M.P., A.L., K.G., H.K., M.W.P., U.K. report no conflict of interests.

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