US2012288525A1PendingUtilityA1

Pharmaceutical compositions comprising attenuated plasmodium sporozoites and glycolipid adjuvants

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Assignee: CHAKRAVARTY SUMANAPriority: May 11, 2011Filed: May 11, 2012Published: Nov 15, 2012
Est. expiryMay 11, 2031(~4.8 yrs left)· nominal 20-yr term from priority
Inventors:Sumana ChakravartyStephen L. HoffmanMoriya Tsuji
A61P 33/06A61K 9/0019A61K 9/0021A61K 2039/54A61K 2039/522A61K 2039/55511A61K 39/015A61K 39/39Y02A50/30
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Claims

Abstract

Disclosed herein are pharmaceutical compositions comprising Plasmodium sporozoite-stage parasites and compatible glycolipid adjuvants useful in vaccines for preventing or reducing the risk of malaria. In particular, human host range Plasmodium and analogues of α-galactosylceramide (α-GalCer), a ligand for natural killer T (NKT) cells, are combined in pharmaceutical compositions, which are useful as vaccines against malaria. Methods of use are also provided.

Claims

exact text as granted — not AI-modified
1 . A pharmaceutical composition comprising one or more species of live  Plasmodium  sporozoite-stage parasites, an excipient, and a glycolipid adjuvant, wherein said adjuvant is represented by the structure of formula 1; 
       
         
           
           
               
               
           
         
         wherein R is selected from the group consisting of: R═(CH 2 ) 5 Ph(p-OMe); R═(CH 2 ) 7 Ph(p-OMe); R═(CH 2 ) 7 Ph(p-F); R═(CH 2 ) 10 Ph(p-F); and R═(CH 2 ) 10 Ph(p-CF 3 ). 
       
     
     
         2 . The pharmaceutical composition of  claim 1  wherein R═(CH 2 ) 10 Ph(p-F). 
     
     
         3 . The pharmaceutical composition of  claim 1  wherein said species are selected from the group consisting of:  P. falciparum, P. vivax, P. ovale, P. knowlesi, P. malariae , and  P. yoelii.    
     
     
         4 . The pharmaceutical composition of  claim 3  wherein said species comprises  P. falciparum.    
     
     
         5 . The pharmaceutical composition of  claim 3  wherein said sporozoite-stage parasites are attenuated. 
     
     
         6 . A method of reducing the risk of malaria in a host exposed to pathogenic  Plasmodium  species parasites, said method comprising administration of one or more doses of a pharmaceutical composition to said host prior to said exposure, wherein said pharmaceutical composition comprises one or more species of live attenuated  Plasmodium  sporozoite-stage parasites and an excipient; and wherein a glycolipid adjuvant represented by the structure of formula 1 is co-administered; 
       
         
           
           
               
               
           
         
         wherein R is selected from the group consisting of: R═(CH 2 ) 5 Ph(p-OMe); R═(CH 2 ) 7 Ph(p-OMe); R═(CH 2 ) 7 Ph(p-F); R═(CH 2 ) 10 Ph(p-F); R═(CH 2 ) 10 Ph(p-CF 3 ). 
       
     
     
         7 . The method of  claim 6  wherein R═(CH 2 ) 10 Ph(p-F). 
     
     
         8 . The method of  claim 6  wherein said host is a mammalian host. 
     
     
         9 . The method of  claim 8  wherein said host is a human host. 
     
     
         10 . The method of  claim 6  wherein said one or more doses comprise no more than 150,000 sporozoites. 
     
     
         11 . The method of  claim 10  wherein said one or more doses comprise no more than 50,000 sporozoites. 
     
     
         12 . The method of  claim 11  wherein said one or more doses comprise no more than 25,000 sporozoites. 
     
     
         13 . The method of  claim 6  wherein the number of doses is no more than 3. 
     
     
         14 . The method of  claim 13  wherein the number of doses is no more than 2. 
     
     
         15 . The method of  claim 14  wherein the number of doses is no more than 1. 
     
     
         16 . The method of  claim 6  wherein said  Plasmodium  species of said pharmaceutical composition are selected from the group consisting of:  P. falciparum, P. vivax, P. ovale, P. knowlesi , and  P. malariae.    
     
     
         17 . The method of  claim 16  wherein said  Plasmodium  species of said pharmaceutical composition comprises  P. falciparum.    
     
     
         18 . The method of  claim 6  wherein said pharmaceutical composition is administered by a parenteral route chosen from the group consisting of intravenous, intramuscular, intradermal, and subcutaneous. 
     
     
         19 . A malaria vaccine comprising one or more species of live  Plasmodium  sporozoite-stage parasites, an excipient, and a glycolipid adjuvant, wherein said adjuvant is represented by the structure of formula 1; 
       
         
           
           
               
               
           
         
         wherein R is selected from the group consisting of: R═(CH 2 ) 5 Ph(p-OMe); R═(CH 2 ) 7 Ph(p-OMe); R═(CH 2 ) 7 Ph(p-F); R═(CH 2 ) 10 Ph(p-F); and R═(CH 2 ) 10 Ph(p-CF3). 
       
     
     
         20 . The vaccine of  claim 19  wherein R═(CH 2 ) 10 Ph(p-F). 
     
     
         21 . The vaccine of  claim 19  wherein said species are selected from the group consisting of:  P. falciparum, P. vivax, P. ovale, P. knowlesi, P. malariae , and  P. yoelii.    
     
     
         22 . The vaccine of  claim 21  wherein said species comprises  P. falciparum.    
     
     
         23 . The vaccine of  claim 19  wherein said sporozoite-stage parasites are attenuated. 
     
     
         24 . A method of reducing the risk of malaria in a host exposed to pathogenic  Plasmodium  species parasites, said method comprising administration of one or more doses of a pharmaceutical composition to said host prior to said exposure, wherein said pharmaceutical composition comprises one or more species of live  Plasmodium  sporozoite-stage parasites and an excipient; and, wherein
 a glycolipid adjuvant is co-administered, wherein said adjuvant is represented by the structure of formula 1;   
       
         
           
           
               
               
           
         
         wherein R is selected from the group consisting of: R═(CH 2 ) 5 Ph(p-OMe); R═(CH 2 ) 7 Ph(p-OMe); R═(CH 2 ) 7 Ph(p-F); R═(CH 2 ) 10 Ph(p-P); R═(CH 2 ) 10 Ph(p-CF 3 ); 
         and wherein an antimalarial drug was previously administered such that the concentration of said drug in the bloodstream of said host is sufficient to prevent the clinical manifestations of malaria. 
       
     
     
         25 . The method of  claim 24  wherein R═(CH 2 ) 10 Ph(p-F). 
     
     
         26 . The method of  claim 24  wherein said host is a mammalian host. 
     
     
         27 . The method of  claim 26  wherein said host is a human host. 
     
     
         28 . The method of  claim 24  wherein said antimalarial drug is chloroquine. 
     
     
         29 . The method of  claim 24  wherein said one or more doses comprise no more than 150,000 sporozoites. 
     
     
         30 . The method of  claim 29  wherein said one or more doses comprise no more than 50,000 sporozoites. 
     
     
         31 . The method of  claim 30  wherein said one or more doses comprise no more than 25,000 sporozoites. 
     
     
         32 . The method of  claim 24  wherein the number of doses is no more than 3. 
     
     
         33 . The method of  claim 32  wherein the number of doses is no more than 2. 
     
     
         34 . The method of  claim 33  wherein the number of doses is no more than 1. 
     
     
         35 . The method of  claim 24  wherein said  Plasmodium  species of said pharmaceutical composition are selected from the group consisting of:  P. falciparum, P. vivax, P. ovate, P. knowlesi , and  P. malariae.    
     
     
         36 . The method of  claim 35  wherein said  Plasmodium  species of said pharmaceutical composition comprises  P. falciparum.    
     
     
         37 . The method of  claim 24  wherein said pharmaceutical composition is administered by a parenteral route chosen from the group consisting of intravenous, intramuscular, intradermal, and subcutaneous.

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