title: Transcutaneous immunization with Clostridium difficile toxoid A induces systemic and mucosal immune responses and toxin A-neutralizing antibodies in mice.
abstract: Clostridium difficile is the leading cause of nosocomial infectious diarrhea. C. difficile produces two toxins (A and B), and systemic and mucosal anti-toxin A antibodies prevent or limit C. difficile-associated diarrhea. To evaluate whether transcutaneous immunization with formalin-treated C. difficile toxin A (CDA) induces systemic and mucosal anti-CDA immune responses, we transcutaneously immunized three cohorts of mice with CDA with or without immunoadjuvantative cholera toxin (CT) on days 0, 14, 28, and 42. Mice transcutaneously immunized with CDA and CT developed prominent anti-CDA and anti-CT immunoglobulin G (IgG) and IgA responses in serum and anti-CDA and anti-CT IgA responses in stool. Sera from immunized mice were able to neutralize C. difficile toxin A activity in an in vitro cell culture assay. CDA itself demonstrated adjuvant activity and enhanced both serum and stool anti-CT IgA responses. Our results suggest that transcutaneous immunization with CDA toxoid may be a feasible immunization strategy against C. difficile, an important cause of morbidity and mortality against which current preventative strategies are failing.
authors: Division of Infectious Diseases, Massachusetts General Hospital, Jackson 504, 55 Fruit Street, Boston, MA 02114, USA. etryan@partners.org
authors: Chandrabali
authors: C
authors: Ghose
authors: Anuj
authors: A
authors: Kalsy
authors: Alaullah
authors: A
authors: Sheikh
authors: Julianne
authors: J
authors: Rollenhagen
authors: Manohar
authors: M
authors: John
authors: John
authors: J
authors: Young
authors: Sean M
authors: SM
authors: Rollins
authors: Firdausi
authors: F
authors: Qadri
authors: Stephen B
authors: SB
authors: Calderwood
authors: Ciaran P
authors: CP
authors: Kelly
authors: Edward T
authors: ET
authors: Ryan
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis / Q000276:immunology*; D001427:Bacterial Toxins / Q000008:administration & dosage* / Q000276:immunology; D016360:Clostridioides difficile / Q000737:chemistry*; D004768:Enterotoxins / Q000008:administration & dosage* / Q000276:immunology; D018928:Immunity, Mucosal; D007114:Immunization; D051379:Mice; D009092:Mucous Membrane / Q000276:immunology; D009500:Neutralization Tests; D014121:Toxoids / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D004768:Enterotoxins; D014121:Toxoids; C041348:tcdA protein, Clostridium difficile