title: Immunogenicity and protective efficacy of recombinant Clostridium difficile flagellar protein FliC.
abstract: Clostridium difficile is a Gram-positive bacillus and is the leading cause of toxin-mediated nosocomial diarrhea following antibiotic use. C. difficile flagella play a role in colonization, adherence, biofilm formation, and toxin production, which might contribute to the overall virulence of certain strains. Human and animal studies indicate that anti-flagella immune responses may play a role in protection against colonization by C. difficile and subsequent disease outcome. Here we report that recombinant C. difficile flagellin (FliC) is immunogenic and protective in a murine model of C. difficile infection (CDI) against a clinical C. difficile strain, UK1. Passive protection experiments using anti-FliC polyclonal serum in mice suggest this protection to be antibody-mediated. FliC immunization also was able to afford partial protection against CDI and death in hamsters following challenge with C. difficile 630Δerm. Additionally, immunization against FliC does not have an adverse effect on the normal gut flora of vaccinated hamsters as evidenced by comparing the fecal microbiome of vaccinated and control hamsters. Therefore, the use of FliC as a vaccine candidate against CDI warrants further testing.
authors.affiliation: Aaron Diamond AIDS Research Center, New York, NY 10075, USA.
authors.forename: Chandrabali
authors.initials: C
authors.lastname: Ghose
authors.affiliation: Aaron Diamond AIDS Research Center, New York, NY 10075, USA.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Eugenis
authors.affiliation: Tufts University, Cummings School of Veterinary Medicine, North Grafton, MA 01536, USA.
authors.forename: Xingmin
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Adrianne N
authors.initials: AN
authors.lastname: Edwards
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Shonna M
authors.initials: SM
authors.lastname: McBride
authors.affiliation: Departments of Pathology and Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: David T
authors.initials: DT
authors.lastname: Pride
authors.affiliation: Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Ciarán P
authors.initials: CP
authors.lastname: Kelly
authors.affiliation: Aaron Diamond AIDS Research Center, New York, NY 10075, USA.|The Rockefeller University, New York, NY 10065, USA.
authors.forename: David D
authors.initials: DD
authors.lastname: Ho
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D016360:Clostridioides difficile / Q000737:chemistry / Q000166:cytology / Q000235:genetics / Q000276:immunology*; D003015:Clostridium Infections / Q000517:prevention & control*; D006224:Cricetinae; D003428:Cross Infection / Q000382:microbiology / Q000517:prevention & control; D004195:Disease Models, Animal; D005243:Feces / Q000382:microbiology; D005260:Female; D005407:Flagella / Q000737:chemistry / Q000276:immunology*; D005408:Flagellin / Q000235:genetics / Q000276:immunology*; D000069196:Gastrointestinal Microbiome; D006801:Humans; D007114:Immunization; D007116:Immunization, Passive; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D011994:Recombinant Proteins; D005408:Flagellin
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