A Novel, Orally Delivered Antibody Therapy and Its Potential to Prevent Clostridioides difficile Infection in Pre-clinical Models
| Autor: | William Spitall, Caroline H. Chilton, April K. Roberts, Ines B Moura, Duncan Ewin, Clifford C. Shone, Emma Clark, Mark H. Wilcox, Hannah C Harris, Anthony M. Buckley, Rossen Donev, Oktawia J Polak, Michael Smith, Joanna L. Giles |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Microbiology (medical)
genetic structures lcsh:QR1-502 Hamster Pharmacology medicine.disease_cause Microbiology lcsh:Microbiology 03 medical and health sciences In vivo medicine 030304 developmental biology Original Research 0303 health sciences Gastrointestinal tract biology 030306 microbiology Toxin business.industry Antibody titer in vitro human gut model of CDI In vitro formulation protecting antibodies from digestion/inactivation biology.protein oral antibodies Vancomycin Antibody business in vivo hamster model of CDI Clostridioides difficile infection (CDI) immunotherapy of CDI medicine.drug |
| Zdroj: | Frontiers in Microbiology Frontiers in Microbiology, Vol 11 (2020) |
| ISSN: | 1664-302X |
| Popis: | Clostridioides difficile infection (CDI) is a toxin-mediated infection in the gut and a major burden on healthcare facilities worldwide. We rationalized that it would be beneficial to design an antibody therapy that is delivered to, and is active at the site of toxin production, rather than neutralizing the circulating and luminal toxins after significant damage of the layers of the intestines has occurred. Here we describe a highly potent therapeutic, OraCAb, with high antibody titers and a formulation that protects the antibodies from digestion/inactivation in the gastrointestinal tract. The potential of OraCAb to prevent CDI in an in vivo hamster model and an in vitro human colon model was assessed. In the hamster model we optimized the ratio of the antibodies against each of the toxins produced by C. difficile (Toxins A and B). The concentration of immunoglobulins that is effective in a hamster model of CDI was determined. A highly significant difference in animal survival for those given an optimized OraCAb formulation versus an untreated control group was observed. This is the first study testing the effect of oral antibodies for treatment of CDI in an in vitro gut model seeded with a human fecal inoculum. Treatment with OraCAb successfully neutralized toxin production and did not interfere with the colonic microbiota in this model. Also, treatment with a combination of vancomycin and OraCAb prevented simulated CDI recurrence, unlike vancomycin therapy alone. These data demonstrate the efficacy of OraCAb formulation for the treatment of CDI in pre-clinical models. |
| Databáze: | OpenAIRE |
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