Compositions and Methods for Immunizing Against C. Difficile

Abstract

This disclosure relates to methods for eliciting an immune response against C. difficile toxin A and toxin B in an adult human subject. The subject may be at risk for a primary symptomatic C. difficile infection. In some embodiments, a method is for eliciting an immune response against C. difficile toxin A and toxin B in an adult human subject at risk for a primary symptomatic C. difficile infection, and comprises administering to the subject a composition comprising C. difficile toxoid A and toxoid B at least three times, each administration being about seven days apart.

1 . A method for eliciting an immune response against  C. difficile  toxin A and toxin B in an adult human subject at risk for a primary symptomatic  C. difficile  infection, the method comprising administering to the subject a composition comprising  C. difficile  toxoid A and toxoid B at least three times, each administration being about seven days apart. 
     
     
         2 . The method of  claim 1  wherein the immune response elicited is sufficient to prevent and/or reduce a primary symptomatic  C. difficile  infection in the adult human subject. 
     
     
         3 . The method of  claim 1  wherein the immune response elicited is sufficient to prevent the onset of a symptomatic  C. difficile  infection in the adult human subject. 
     
     
         4 . The method of any one of  claims 1 - 3  wherein the second administration is about 7 days after the first administration and the third administration is about 30 days after the first or second administration. 
     
     
         5 . The method of  claim 4  wherein the third administration is about 30 days after the first administration. 
     
     
         6 . The method of any one of  claims 1 - 3  wherein the second administration is about 7 days after the first administration and the third administration is about 180 days after the first or second administration. 
     
     
         7 . The method of  claim 6  wherein the third administration is about 180 days after the first administration. 
     
     
         8 . The method of any one of  claims 1 - 7  wherein the composition comprises each of  C. difficile  toxoid A and toxoid B, having a purity of at least about 90% or greater, in a ratio of about 3:1 to about 1:1. 
     
     
         9 . The method of  claim 8  wherein the ratio of  C. difficile  toxoid A and toxoid B is about 3:2. 
     
     
         10 . The method of any one of  claims 1 - 9  wherein the composition comprises a combined total of  C. difficile  toxoid A and toxoid B of about 40 to 500 μg. 
     
     
         11 . The method of  claims 1 - 10  wherein the composition comprises an adjuvant. 
     
     
         12 . The method of  claim 11  wherein the composition comprises an aluminum adjuvant. 
     
     
         13 . The method of any one of  claims 1 - 12  wherein the subject at risk is at least 40 years of age and:
 (i) has had, in the 12 month period before the first administration, at least 2 hospital stays, each lasting at least about 24 or 72 hours, and has received systemic (not topical) antibiotics, or 
 (ii) is anticipated to have an in-patient hospitalization for a planned surgical procedure within 60 days of the first administration. 
 
     
     
         14 . The method of  claim 13 , wherein the anticipated hospitalization is planned to be for at least about 24 or 72 hours and is for a surgery involving at least one of the following systems:
 (i) kidney/bladder/urinary system;   (ii) musculoskeletal system;   (iii) respiratory system;   (iv) circulatory system; and   (v) central nervous system.   
     
     
         15 . The method of any one of  claims 1 - 14  wherein the adult human subject is at least about 65 years or older. 
     
     
         16 . The method of any one of  claims 1 - 15  wherein an immune response against  C. difficile  toxin A and/or toxin B is sustained for at least about 60 days. 
     
     
         17 . The method of  claim 16  wherein an immune response against  C. difficile  toxin A and/or toxin B is sustained for at least about 210 days. 
     
     
         18 . The method of  claim 17  wherein an immune response against  C. difficile  toxin A and/or toxin B is sustained for at least about 1000 days. 
     
     
         19 . Using a composition comprising  C. difficile  toxoid A and toxoid B in producing a medicament for eliciting an immune response against  C. difficile  toxin A and toxin B in an adult human subject at risk for a primary symptomatic  C. difficile  infection by administering the composition to the subject at least three times, each administration being about seven days apart. 
     
     
         20 . The use of  claim 19  wherein the immune response elicited is sufficient to prevent and/or reduce the risk of a primary symptomatic  C. difficile  infection in the adult human subject. 
     
     
         21 . The use of  claim 19  wherein the immune response elicited is sufficient to prevent the onset of a symptomatic  C. difficile  infection in the adult human subject. 
     
     
         22 . The use of any one of  claims 19 - 21  wherein the second administration is about 7 days after the first administration and the third administration is about 30 days after the first or second administration. 
     
     
         23 . The use of  claim 22  wherein the third administration is about 30 days after the first administration. 
     
     
         24 . The use of any one of  claims 19 - 21  wherein the second administration is about 7 days after the first administration and the third administration is about 180 days after the first or second administration. 
     
     
         25 . The use of  claim 24  wherein the third administration is about 180 days after the first administration. 
     
     
         26 . The use of any one of  claims 19 - 25  wherein the composition comprises each of  C. difficile  toxoid A and toxoid B, having a purity of at least about 90% or greater, in a ratio of about 3:1 to about 1:1. 
     
     
         27 . The use of  claim 26  wherein the ratio of  C. difficile  toxoid A and toxoid B is about 3:2. 
     
     
         28 . The use of any one of  claims 19 - 27  wherein the composition comprises a combined total of  C. difficile  toxoid A and toxoid B of about 40 to 500 μg. 
     
     
         29 . The use of any one of  claims 19 - 28  wherein the composition comprises an adjuvant. 
     
     
         30 . The use of  claim 29  wherein the composition comprises an aluminum adjuvant. 
     
     
         31 . The use of any one of  claims 19 - 30  wherein the subject at risk is at least 40 years of age and:
 (i) has had, in the 12 month period before the first administration, at least 2 hospital stays, each lasting at least about 24 or 72 hours, and has received systemic (not topical) antibiotics, or 
 (ii) is anticipated to have an in-patient hospitalization for a planned surgical procedure within 60 days of the first administration. 
 
     
     
         32 . The use of  claim 31 , wherein the anticipated hospitalization is planned to be for at least about 24 or 72 hours and is for a surgery involving at least one of the following systems: (i) kidney/bladder/urinary system; (ii) musculoskeletal system; (iii) respiratory system; (iv) circulatory system; and (v) central nervous system. 
     
     
         33 . The use of any one of  claims 19 - 32  wherein the adult human subject is at least about 65 years or older. 
     
     
         34 . The use of any one of  claims 19 - 33  wherein an immune response against  C. difficile  toxin A and/or toxin B is sustained for at least about 60 days. 
     
     
         35 . The use of  claim 34  wherein an immune response against  C. difficile  toxin A and/or toxin B is sustained for at least about 210 days. 
     
     
         36 . The use of  claim 34  wherein an immune response against  C. difficile  toxin A and/or toxin B is sustained for at least about 1000 days. 
     
     
         37 . A composition comprising  C. difficile  toxoid A and toxoid B for use in a method for eliciting an immune response against  C. difficile  toxin A and toxin B in a human subject, the method comprising administering the subject the composition at least three times, each administration being about 7 days apart.