Immunization Against Clostridium Difficile Disease
The invention provides active and passive immunization methods for preventing and treating Clostridium difficile infection, which involve percutaneous administration of C. difficile toxin-neutralizing polyclonal immune globulin, C. difficile toxoids, or combinations thereof. Also provided by the invention are C. difficile toxoids, C. difficile toxin-neutralizing polyclonal immune globulin, and methods of identifying subjects that produce C. difficile toxin-neutralizing polyclonal immune globulin.
1 . A vaccine composition comprising a clostridial toxoid and an aluminum adjuvant.
2 . The vaccine of claim 1 , wherein the clostridial toxoid comprises Clostridium difficile Toxoid A and Toxoid B.
3 . The vaccine composition of claim 1 , wherein the aluminum adjuvant is selected from the group consisting of aluminum hydroxide, aluminum phosphate, and aluminum hydroxy phosphate.
4 . The vaccine composition of claim 1 , wherein the composition further comprises 0.012-0.020% formaldehyde.
5 . A vaccine composition comprising (i) a toxoid of Clostridium difficile Toxins A and B, (ii) an aluminum adjuvant, and (iii) 0.012-0.020% formaldehyde.
6 . A vaccine composition comprising (i) a toxoid of Clostridium difficile Toxins A and B, and (ii) an aluminum adjuvant.
7 . A method of preventing or treating symptomatic Clostridium difficile disease in a human patient, the method comprising percutaneously administering to the human patient (i) a clostridial toxin or toxoid, and (ii) an aluminum adjuvant.
8 . The method of claim 7 , wherein the aluminum adjuvant is selected from the group consisting of aluminum hydroxide, aluminum phosphate, and aluminum hydroxy phosphate.
9 . The method of claim 7 , wherein the toxin or toxoid is a Clostridium difficile toxin or toxoid.
10 . The method of claim 9 , wherein the Clostridium difficile toxin or toxoid comprises Clostridium difficile Toxoid A and Toxoid B.
11 . The method of claim 7 , wherein the patient has or is at risk of developing recurrent Clostridium difficile disease.
12 . The method of claim 7 , wherein the clostridial toxin or toxoid is intramuscularly, intravenously, or subcutaneously administered to the human patient.
13 . The method of claim 7 , wherein the patient does not have, but is at risk of developing, symptomatic Clostridium difficile disease.
14 . The method of claim 7 , wherein the patient has symptomatic Clostridium difficile disease.
15 . The method of claim 7 , wherein the administered clostridial toxin or toxoid and the aluminum adjuvant are present in a single composition.
16 . The method of claim 15 , wherein the composition further comprises 0.012-0.020% formaldehyde.
17 . A method of preventing or treating symptomatic Clostridium difficile infection in a human patient, the method comprising percutaneously administering to the human patient a vaccine composition comprising (i) a toxoid of Clostridium difficile Toxins A and B, (ii) an aluminum adjuvant, and (iii) 0.012-0.020% formaldehyde.
18 . A method of preventing or treating symptomatic Clostridium difficile infection in a human patient, the method comprising percutaneously administering to the human patient a vaccine composition comprising (i) a toxoid of Clostridium difficile Toxins A and B, and (ii) an aluminum adjuvant.