title: Systemically administered IgG anti-toxin antibodies protect the colonic mucosa during infection with Clostridium difficile in the piglet model.
abstract: The use of anti-toxin human monoclonal antibodies (HMab) as treatment for C. difficile infection has been investigated in animal models and human clinical trials as an alternative to or in combination with traditional antibiotic therapy. While HMab therapy appears to be a promising option, how systemically administered IgG antibodies protect the colonic mucosa during Clostridium difficile infection is unknown. Using the gnotobiotic piglet model of Clostridium difficile infection, we administered a mixture of anti-TcdA and anti-TcdB HMabs systemically to piglets infected with either pathogenic or non-pathogenic C. difficile strains. The HMabs were present throughout the small and large intestinal tissue of both groups, but significant HMabs were present in the lumen of the large intestines only in the pathogenic strain-infected group. Similarly, HMabs measured in the large intestine over a period of 2-4 days following antibody administration were not significantly different over time in the gut mucosa among the groups, but concentrations in the lumen of the large intestine were again consistently higher in the pathogenic strain-infected group. These results indicate that systemically administered HMab IgG reaches the gut mucosa during the course of CDI, protecting the host against systemic intoxication, and that leakage through the damaged colon likely protects the mucosa from further damage, allowing initiation of repair and recovery.
authors.affiliation: Department of Infectious Disease and Global Health, Tufts Cummings School of Veterinary Medicine, North Grafton, Massachusetts, United States of America.
authors.forename: Ocean R
authors.initials: OR
authors.lastname: Cohen
authors.affiliation: Department of Infectious Disease and Global Health, Tufts Cummings School of Veterinary Medicine, North Grafton, Massachusetts, United States of America.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Steele
authors.affiliation: Department of Infectious Disease and Global Health, Tufts Cummings School of Veterinary Medicine, North Grafton, Massachusetts, United States of America.
authors.forename: Quanshun
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Infectious Disease and Global Health, Tufts Cummings School of Veterinary Medicine, North Grafton, Massachusetts, United States of America.
authors.forename: Diane J
authors.initials: DJ
authors.lastname: Schmidt
authors.affiliation: Department of Infectious Disease and Global Health, Tufts Cummings School of Veterinary Medicine, North Grafton, Massachusetts, United States of America.
authors.forename: Yuankai
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Infectious Disease and Global Health, Tufts Cummings School of Veterinary Medicine, North Grafton, Massachusetts, United States of America.
authors.forename: Philip E S
authors.initials: PE
authors.lastname: Hamel
authors.affiliation: Department of Infectious Disease and Global Health, Tufts Cummings School of Veterinary Medicine, North Grafton, Massachusetts, United States of America.
authors.forename: Gillian
authors.initials: G
authors.lastname: Beamer
authors.affiliation: Department of Infectious Disease and Global Health, Tufts Cummings School of Veterinary Medicine, North Grafton, Massachusetts, United States of America.
authors.forename: Bingling
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Infectious Disease and Global Health, Tufts Cummings School of Veterinary Medicine, North Grafton, Massachusetts, United States of America.
authors.forename: Saul
authors.initials: S
authors.lastname: Tzipori
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000992:Antitoxins / Q000008:administration & dosage*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000276:immunology; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors / Q000276:immunology; D016360:Clostridioides difficile / Q000276:immunology*; D003106:Colon / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D004761:Enterocolitis, Pseudomembranous / Q000401:mortality / Q000473:pathology* / Q000517:prevention & control*; D004768:Enterotoxins / Q000037:antagonists & inhibitors / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage*; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology*; D013552:Swine
chemical_list: D000911:Antibodies, Monoclonal; D000992:Antitoxins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; D007074:Immunoglobulin G; C041348:tcdA protein, Clostridium difficile; C031815:toxB protein, Clostridium difficile