Anti-adhesin based passive immunoprophlactic

Abstract

The invention relates to an immunogenic composition and method of the immunogenic composition for the production and administration of a passive immunoprophylactic against enterotoxigenic Escherichia coli. The immunoprophylactic is made collecting anti-adhesin in the colostrum or milk of vaccinated domesticated animals such as cows. The immunoprophylactic is administered either as a dietary supplement or in capsular or tablet form.

1 . A pharmaceutical composition, wherein said composition is composed of colostrums or milk immunoglobulin against enterotoxigenic  Escherichia coli  adhesin molecules.  
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein said adhesin molecules are derived from Class 5 fimbriae.  
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the said adhesin molecule is one or more fimbrial minor subunits selected from the group consisting of CfaE, CsfD, CsuD, CooD, CosD, CsdD, CsbD and CotD.  
     
     
         4 . A method of producing the anti-enterotoxigenic  Escherichia coli  composition of  claim 1  comprising the steps: 
 a. administering to a milk producing domesticated animal an immunogen composed of one or more Class five  Escherichia coli  fimbrial adhesins or fragments thereof;    b. collecting immunoglobulin containing colostrum or milk from said domesticated animal.    
     
     
         5 . The method of  claim 4 , wherein the concentration of anti-adhesin immunoglobulin in said collected colostrum or milk is adjusted to 0.1 g IgG per dose to 20.0 g of IgG per dose of said passive prophylactic.  
     
     
         6 . The method of  claim 4 , wherein said domesticated animal is a cow or goat.  
     
     
         7 . The method of  claim 4 , wherein said adhesin is selected from the group consisting of CfaE, CsfD, CsuD, CooD, CosD, CsdD, CsbD and CotD.  
     
     
         8 . The method of  claim 4 , wherein said immunogen also comprises one or more  Escherichia coli  major fimbrial subunit is selected from the group consisting of CfaB, CsfA, CsuA1, CsuA2, CooA, CosA, CsbA, CsdA and CotB.  
     
     
         9 . The method of  claim 4 , wherein said immunogen is an  Escherichia coli  fimbrial adhesin domain and polyhistidine tail fusion polypeptide composed of the amino acid sequence selected from the group consisting of SEQ ID No. 35, SEQ ID No. 36 and SEQ ID No. 37.  
     
     
         10 . The method of  claim 8 , wherein said  Escherichia coli  fimbrial adhesin is linked at its C-terminus to a linker which is operatively linked at its C-terminus to said  Escherichia coli  major fimbrial subunit.  
     
     
         11 . The method of  claim 10 , wherein said  Escherichia coli  fimbrial adhesin is a monomer or polymer of adhesin polypeptides.  
     
     
         12 . The method of  claim 10 , wherein said linker is composed of the amino acid sequence selected from the group consisting of SEQ ID No. 10, 12 and 13.  
     
     
         13 . The method of  claim 10 , wherein said fimbrial adhesin is selected from the group consisting of CfaE, CsfD, CsuD, CooD, CosD, CsdD, CsbD and CotD.  
     
     
         14 . The method of  claim 10 , wherein said major fimbrial subunit is selected from the group consisting of CfaB, CsfA, CsuA1, CsuA2, CooA, CosA, CsbA, CsdA and CotB.  
     
     
         15 . The method of  claim 10 , wherein said immunogen contains a polyhistidine tail linked at the C-terminus of said  Escherichia coli  major fimbrial subunit.  
     
     
         16 . The method of  claim 13 , wherein said fimbrial adhesin is the amino acid sequence selected from the group consisting of SEQ ID No. 1, SEQ ID No. 22, SEQ ID No. 27, SEQ ID No.28, SEQ ID No.29, SEQ ID No.30, SEQ ID No.31, SEQ ID No.32 or fragments thereof.  
     
     
         17 . The method of  claim 13 , wherein said CfaE is composed of the amino acid sequence of SEQ ID No.11 encoded by all or a portion of the nucleotide sequence of SEQ ID No. 18 or fragment thereof.  
     
     
         18 . The method of  claim 13 , wherein said CsbD is composed of the amino acid sequence of SEQ ID No.22 encoded by the nucleotide sequence of SEQ ID No.19 or fragment thereof.  
     
     
         19 . The method of  claim 13 , wherein said CotD is composed of the amino acid sequence of SEQ ID No.32 or fragment thereof.  
     
     
         20 . The method of  claim 13 , wherein said  Escherichia coli  fimbrial adhesin is composed of amino acids 58-185 of the sequence selected from the group consisting of SEQ ID No. 11, SEQ ID No.22, SEQ ID No.27, SEQ ID No.28, SEQ ID No.29, SEQ ID No.30, SEQ ID No.31, SEQ ID No.32.  
     
     
         21 . The method of  claim 13 , wherein said  Escherichia coli  fimbrial adhesin is composed of amino acids 14-205 of the sequence selected from the group consisting of SEQ ID No. 11, SEQ ID No.22, SEQ ID No.27, SEQ ID No.28, SEQ ID No.29, SEQ ID No.30, SEQ ID No.31, SEQ ID No.32.  
     
     
         22 . The method of  claim 14 , wherein said major fimbrial subunit is the amino acid sequence selected from the group consisting of SEQ ID No.1, SEQ ID No.2, SEQ ID No.3, SEQ ID No.4, SEQ ID No.5, SEQ ID No.6, SEQ ID No.7, SEQ ID No.8, and SEQ ID No.9.  
     
     
         23 . The method of  claim 15 , wherein said immunogen is a fusion polypeptide containing a polyhistidine tail composed of the amino acid sequence selected from the group consisting of SEQ ID No. 23 encoded by SEQ ID No. 24, SEQ ID No. 25 encoded by SEQ ID No.26 and SEQ ID No.34.  
     
     
         24 . The method of  claim 17 , wherein said major fimbrial subunit is CfaB with a polypeptide sequence of SEQ ID No. 1 encoded by nucleotide sequence SEQ ID No. 20.  
     
     
         25 . The method of  claim 18 , wherein said major fimbrial subunit is CsbA with a polypeptide sequence of SEQ ID No. 7 encoded by nucleotide sequence SEQ ID No. 21.  
     
     
         26 . The method of  claim 19 , wherein said major fimbrial subunit is CotA with a polypeptide sequence of SEQ ID. No. 9.  
     
     
         27 . A method of conferring passive immunity to enterotoxigenic  Escherichia coli  comprising: 
 a. administering to a milk producing animal an immunogen composed of native or recombinant  Escherichia coli  adhesin so as to induce adhesin specific antibody in the colostrums or milk of said milk producing animals;    b. collecting said colostrum or milk product containing said adhesin specific antibody;    c. administering a dose of said bovine milk anti-adhesin immunoglobulin by ingestion wherein said dose is 0.1 g IgG per dose to 20.0 g of IgG per dose.    
     
     
         28 . The method of  claim 27 , wherein said dose is administered by mixing said colostrum or milk anti-adhesin immunoglobulin in a beverage or food.  
     
     
         29 . The method of  claim 27 , wherein said dose is administered in capsule or tablet form.