US2010330074A1PendingUtilityA1

Use of saccharides cross-reactive with bacillus anthracis spore glycoprotein as a vaccine against anthrax

Assignee: KUBLER-KIELB JOANNAPriority: Feb 19, 2008Filed: Feb 17, 2009Published: Dec 30, 2010
Est. expiryFeb 19, 2028(~1.6 yrs left)· nominal 20-yr term from priority
A61K 39/0208A61K 2039/6081A61K 2039/521C07H 5/04A61K 47/643A61K 39/104A61K 39/07C07H 3/06A61P 31/04A61K 47/646A61K 39/00
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Claims

Abstract

Provided are immunogenic compositions and methods for eliciting an immune response against B. anthracis and other bacteria that contain 3-methyl-3-hydroxybutyrate- or 3-hydroxybutyrate-substituted saccharides. Conjugates of 3-methyl-3-hydroxybutyrate- or 3-hydroxybutyrate-substituted saccharides elicit an effective immune response against B. anthracis spores in mammalian hosts to which the conjugates are administered.

Claims

exact text as granted — not AI-modified
1 . A pharmaceutical composition comprising at least one immunogenic agent that is cross-reactive with  B. anthracis,  wherein the immunogenic agent is selected from:
 (a) at least one compound comprising:   
       
         
           
           
               
               
           
         
         (b) an isolated  B. anthracis  antigenic component from  Shewanella  or  P. syringae;    
         (c) killed whole cells of  Shewanella  or  P. syringae;  or 
         (d) any combination or mixture of (a)-(c). 
       
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the immunogenic agent is the compound of (a), and the compound of (a) is covalently linked to a polymeric carrier. 
     
     
         3 . The pharmaceutical composition of  claim 2 , wherein the polymeric carrier is a protein. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the immunogenic agent is an isolated  B. anthracis  antigenic component from  Shewanella,  and the component is an isolated capsule from  Shewanella  spp. MR-4. 
     
     
         5 . The pharmaceutical composition of  claim 1 , wherein the immunogenic agent is an isolated  B. anthracis  antigenic component from  P. syringae,  and the component is isolated fimbriae from  P. syringae.    
     
     
         6 . The pharmaceutical composition of  claim 1 , wherein the immunogenic agent is killed whole cells of  Shewanella  spp. MR-4. 
     
     
         7 . The pharmaceutical composition of  claim 1 , wherein the immunogenic agent is killed whole cells of  P. syringae.    
     
     
         8 . A pharmaceutical composition comprising at least one compound that is cross-reactive with  B. anthracis.  wherein the compound comprises 
       
         
           
           
               
               
           
         
         and at least one pharmaceutically acceptable additive. 
       
     
     
         9 . The pharmaceutical composition of  claim 8 , wherein the compound is covalently linked to a polymeric carrier. 
     
     
         10 . The pharmaceutical composition of  claim 9 , wherein the polymeric carrier is a pharmaceutically acceptable protein. 
     
     
         11 . The pharmaceutical composition of  claim 9 , wherein the compound is covalently linked to a carrier selected from bovine serum albumin, recombinant  B. anthracis  protective antigen, recombinant  P. aeruginosa  exotoxin A, tetanus toxoid, diphtheria toxoid, pertussis toxoid,  C. perfringens  toxoid, hepatitis B surface antigen, hepatitis B core antigen, keyhole limpet hemocyanin, or horseshoe crab hemocyanin. 
     
     
         12 . The pharmaceutical composition of  claim 8 , wherein the additive is an adjuvant. 
     
     
         13 . The pharmaceutical composition of  claim 8 , wherein the additive is a pharmaceutically acceptable carrier. 
     
     
         14 . The pharmaceutical composition of  claim 8 , wherein the compound comprises a polysaccharide isolated from a microorganism that is cross-reactive with  B. anthracis.    
     
     
         15 . The pharmaceutical composition of  claim 14 , wherein the microorganism is  Shewanella  or  P. syringae.    
     
     
         16 . The pharmaceutical composition of  claim 14 , wherein the microorganism is  Shewanella  spp. MR-4. 
     
     
         17 . An antibody that is immuno-reactive to a compound comprising 
       
         
           
           
               
               
           
         
       
       wherein the antibody is also immuno-reactive to  B. anthracis  spores. 
     
     
         18 . The antibody of  claim 17 , wherein the antibody is a monoclonal antibody. 
     
     
         19 . A pharmaceutical composition comprising the antibody of  claim 17  and a pharmaceutically acceptable carrier. 
     
     
         20 . A vaccine comprising at least one immunogenic agent that is cross-reactive with  B. anthracis,  wherein the immunogenic agent is selected from:
 (a) at least one compound comprising:   
       
         
           
           
               
               
           
         
         (b) an isolated  B. anthracis  antigenic component from  Shewanella  or  P. syringae;    
         (c) killed whole cells of  Shewanella  or  P. syringae;  or 
         (d) any combination or mixture of (a)-(c). 
       
     
     
         21 . The vaccine of  claim 20 , wherein the immunogenic agent is the compound of (a), and the compound of (a) is covalently linked to a polymeric carrier. 
     
     
         22 . The vaccine of  claim 21 , wherein the polymeric carrier is a protein. 
     
     
         23 . The vaccine of  claim 20 , wherein the immunogenic agent is an isolated  B. anthracis  antigenic component from  Shewanella,  and the component is an isolated capsule from  Shewanella  spp. MR-4. 
     
     
         24 . The vaccine of  claim 20 , wherein the immunogenic agent is an isolated  B. anthracis  antigenic component from  P. syringae,  and the component is isolated fimbriae from  P. syringae.    
     
     
         25 . The vaccine of  claim 20 , wherein the immunogenic agent is killed whole cells of  Shewanella  spp. MR-4. 
     
     
         26 . The vaccine of  claim 20 , wherein the immunogenic agent is killed whole cells of  P. syringae.    
     
     
         27 . An immunogenic conjugate comprising at least one moiety selected from: 
       
         
           
           
               
               
           
         
       
       covalently linked to a carrier, wherein the conjugate elicits an immune response in a subject. 
     
     
         28 . The conjugate of  claim 27 , wherein the moiety is covalently liked to the carrier via the carboxyl group of the —NHCOCH 3  substituent in the first or second moiety, or via the carboxyl group of the —OCH 2 CH(NH 2 )COOH substituent in the third moiety. 
     
     
         29 . The conjugate of  claim 28 , wherein the carrier is selected from bovine serum albumin, recombinant  B. anthracis  protective antigen, recombinant  P. aeruginosa  exotoxin A, tetanus toxoid, diphtheria toxoid, pertussis toxoid,  C. perfringens  toxoid, hepatitis B surface antigen, hepatitis B core antigen, keyhole limpet hemocyanin, or horseshoe crab hemocyanin. 
     
     
         30 . A method of inhibiting a  Bacillus  infection in a subject, the method comprising administering to the subject a therapeutically effective amount of the pharmaceutical composition of  claim 1 . 
     
     
         31 . The method of  claim 30 , wherein the  Bacillus  is  B. anthracis.    
     
     
         32 . The method of  claim 30 , wherein the immunogenic agent is killed whole cells of  Shewanella  or  P. syringae,  and the killed whole cells are administered to a non-human animal that has been, or may have been, exposed to  B. anthracis.    
     
     
         33 . The method of  claim 30 , wherein the subject has been, or may have been, exposed to  B. anthracis.    
     
     
         34 . The method of  claim 30 , wherein the compound is covalently linked to a polymeric carrier. 
     
     
         35 . A method of inhibiting a  Bacillus  infection in a subject, the method comprising administering to the subject a therapeutically effective amount of the vaccine of  claim 20 . 
     
     
         36 . A method of inhibiting a  Bacillus  infection in a subject, the method comprising administering to the subject a therapeutically effective amount of the immunogenic conjugate of  claim 27 . 
     
     
         37 . A method for stimulating an immune response in a subject against  B. anthracis,  comprising
 selecting a subject in need of stimulating an immune response against  B. anthracis;  and   administering to the subject at least one immunogenic agent selected from:   (a) at least one compound comprising:   
       
         
           
           
               
               
           
         
         (b) an isolated  B. anthracis  antigenic component from  Shewanella  or  P. syringae;    
         (c) killed whole cells of  Shewanella  or  P. syringae;  or 
         (d) any combination or mixture of (a)-(c). 
       
     
     
         38 . The method of  claim 37 , wherein the immunogenic agent is the compound of (a), and the compound of (a) is covalently linked to a polymeric carrier. 
     
     
         39 . The method of  claim 38 , wherein the polymeric carrier is a protein. 
     
     
         40 . The method of  claim 37 , wherein the immunogenic agent is an isolated  B. anthracis  antigenic component from  Shewanella,  and the component is an isolated capsule from  Shewanella  spp. MR-4. 
     
     
         41 . The method of  claim 37 , wherein the immunogenic agent is an isolated  B. anthracis  antigenic component from  P. syringae,  and the component is isolated fimbriae from  P. syringae.    
     
     
         42 . The method of  claim 37 , wherein the immunogenic agent is killed whole cells of  Shewanella  spp. MR-4. 
     
     
         43 . The pharmaceutical composition of  claim 37 , wherein the immunogenic agent is killed whole cells of  P. syringae.    
     
     
         44 . A method for screening compounds against  B. anthracis  spores, the method comprising
 providing a compound comprising   
       
         
           
           
               
               
           
         
         adding an antibody that is immuno-reactive with a  B. anthracis  spore, 
         determining a level of reactivity of the compound with the antibody. 
       
     
     
         45 . The method of  claim 44 , wherein the level of reactivity is determined by ELISA.

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