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.
| Original language | English |
|---|---|
| Article number | 98 |
| Journal | Toxins |
| Volume | 11 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 2019 |
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Keywords
- Bovine milk
- Clostridium difficile infection
- Hamster model of CDI
- Prevention of recurrence
- sIgA
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Treatment and prevention of recurrent Clostridium difficile infection with functionalized bovine antibody-enriched whey in a hamster primary infection model. / Heidebrecht, Hans Jürgen; Weiss, William J.; Pulse, Mark; Lange, Anton; Gisch, Karina; Kliem, Heike; Mann, Sacha; Pfaffl, Michael W.; Kulozik, Ulrich; von Eichel-Streiber, Christoph.
In: Toxins, Vol. 11, No. 2, 98, 02.2019.Research output: Contribution to journal › Article
TY - JOUR
T1 - Treatment and prevention of recurrent Clostridium difficile infection with functionalized bovine antibody-enriched whey in a hamster primary infection model
AU - Heidebrecht, Hans Jürgen
AU - Weiss, William J.
AU - Pulse, Mark
AU - Lange, Anton
AU - Gisch, Karina
AU - Kliem, Heike
AU - Mann, Sacha
AU - Pfaffl, Michael W.
AU - Kulozik, Ulrich
AU - von Eichel-Streiber, Christoph
PY - 2019/2
Y1 - 2019/2
N2 - 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.
AB - 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.
KW - Bovine milk
KW - Clostridium difficile infection
KW - Hamster model of CDI
KW - Prevention of recurrence
KW - sIgA
UR - http://www.scopus.com/inward/record.url?scp=85061276337&partnerID=8YFLogxK
U2 - 10.3390/toxins11020098
DO - 10.3390/toxins11020098
M3 - Article
C2 - 30736358
AN - SCOPUS:85061276337
VL - 11
JO - Toxins
JF - Toxins
SN - 2072-6651
IS - 2
M1 - 98
ER -