Immunization Against Clostridium Difficile Disease

Abstract

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.