Transcutaneous immunization with Clostridium difficile toxoid A induces systemic and mucosal immune responses and toxin A-neutralizing antibodies in mice.
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.
Ghose
Chandrabali
C
Division of Infectious Diseases, Massachusetts General Hospital, Jackson 504, 55 Fruit Street, Boston, MA 02114, USA. etryan@partners.org
Kalsy
Anuj
A
Sheikh
Alaullah
A
Rollenhagen
Julianne
J
John
Manohar
M
Young
John
J
Rollins
Sean M
SM
Qadri
Firdausi
F
Calderwood
Stephen B
SB
Kelly
Ciaran P
CP
Ryan
Edward T
ET
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
D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D004768:Enterotoxins; D014121:Toxoids; C041348:tcdA protein, Clostridium difficile