Method for producing and vaccine composition of neisseria meningitidis serogroups a, c, y, and w-135 oligosaccharides conjugated to glycan-free carrier protein

Abstract

A multivalent vaccine composition, a method of producing the multivalent vaccine composition, and an apparatus containing the multivalent vaccine composition. The multivalent vaccine composition may include a mixture. The mixture may include Neisseria meningitides serogroups A, C, Y, and W-135 oligosaccharides conjugated to glycan-free carrier proteins. When administered, the multivalent vaccine composition may provide long-lasting immunity to humans of all age groups, including infants.

I claim: 
     
         1 . A multivalent vaccine composition, comprising: a mixture comprising:
 conjugated Neisseria meningitides serogroup A oligosaccharides, each of the conjugated Neisseria meningitides serogroup A oligosaccharides being conjugated to a first particular glycan-free carrier protein;   conjugated Neisseria meningitides serogroup C oligosaccharides, each of the conjugated Neisseria meningitides serogroup C oligosaccharides being conjugated to a second particular glycan-free carrier protein;   conjugated Neisseria meningitides serogroup Y oligosaccharides, each of the conjugated Neisseria meningitides serogroup Y oligosaccharides being conjugated to a third particular glycan-free carrier protein; and   conjugated Neisseria meningitides serogroup W-135 oligosaccharides, each of the conjugated Neisseria meningitides serogroup W-135 oligosaccharides being conjugated to a fourth particular glycan-free carrier protein.   
     
     
         2 . The multivalent vaccine composition of  claim 1 , wherein at least one of the first, second, third and fourth particular glycan-free carrier proteins is a glycan-free diphtheria toxoid. 
     
     
         3 . The multivalent vaccine composition of  claim 2 , wherein the conjugated Neisseria meningitides serogroup A, C, Y, and W-135 oligosaccharides of the mixture have sizes approximately between 5100 and 9900 Daltons. 
     
     
         4 . The multivalent vaccine composition of  claim 3 , wherein the first, second, third, and fourth particular glycan-free carrier proteins are glycan-free diphtheria toxoid, wherein, with respect to at least one of the conjugated Neisseria meningitides serogroup A, C, Y, and W-135 oligosaccharides of the multivalent vaccine composition, a ratio of a mass of unconjugated Neisseria meningitides serogroup oligosaccharides to a mass of glycan-free diphtheria toxoid is approximately between 1:1 and 1:2. 
     
     
         5 . The multivalent vaccine composition of  claim 3 , wherein the multivalent vaccine composition does not include an adjuvant. 
     
     
         6 . The multivalent vaccine composition of  claim 5 , wherein the glycan-free diphtheria toxoid is not in a detoxified state. 
     
     
         7 . The multivalent vaccine composition of  claim 6 , wherein the glycan-free diphtheria toxoid is glycan-free and formalin-free diphtheriatoxoid. 
     
     
         8 . The multivalent vaccine composition of  claim 6 , wherein the glycan-free diphtheria toxoid is hydrazide-activated glycan-free diphtheriatoxoid. 
     
     
         9 . The multivalent vaccine composition of  claim 1 , wherein each of the first, second, third, and fourth particular glycan-free carrier protein is of a single glycan-free diphtheria toxoid species. 
     
     
         10 . The multivalent vaccine composition of  claim 1 , wherein the multivalent vaccine composition is formulated as an aseptic liquid and is sterilized after formulation. 
     
     
         11 . The multivalent vaccine composition of  claim 10 , wherein the multivalent vaccine composition contains no preservative. 
     
     
         12 . The multivalent vaccine composition of  claim 1 , wherein the multivalent vaccine composition is produced and processed by utilizing animal-component-free reagents and chemicals. 
     
     
         13 . The multivalent vaccine composition of  claim 1 , wherein at least one of the first, second, third, and fourth particular glycan-free carrier proteins is glycan-free and formalin-free diphtheria toxoid. 
     
     
         14 . The multivalent vaccine composition of  claim 1 , wherein the multivalent vaccine composition is a tetravalent vaccine composition. 
     
     
         15 . The multivalent vaccine composition of  claim 1 , wherein the multivalent vaccine composition is a tetravalent vaccine composition and each of the first, second, third, and fourth particular glycan-free carrier proteins is glycan-free and formalin-free diphtheria toxoid. 
     
     
         16 . The multivalent vaccine composition of  claim 1 , wherein the mixture comprises four distinct and collective protein-capsular oligosaccharide monoconjugates of serogroups A, C, Y, and W-135 of Neisseria meningitides. 
     
     
         17 . The multivalent vaccine composition of  claim 1 , wherein the conjugated Neisseria meningitides serogroup A, C, Y, and W-135 oligosaccharides of the mixture have sizes approximately between 5100 and 9900 Daltons. 
     
     
         18 . The multivalent vaccine composition of  claim 17 , wherein the multivalent vaccine composition is configured to provide immunity to humans of all age groups for at least three years. 
     
     
         19 . The multivalent vaccine composition of  claim 17 , wherein the multivalent vaccine composition is configured to provide immunity to infants. 
     
     
         20 . The multivalent vaccine composition of  claim 17 , wherein the multivalent vaccine composition is configured to provide immunity to children less than 2 years of age for at least three years. 
     
     
         21 . The multivalent vaccine composition of  claim 1 , wherein the multivalent vaccine composition is configured to provide immunity to humans of all age groups for at least three years. 
     
     
         22 . The multivalent vaccine composition of  claim 1 , wherein the multivalent vaccine composition is configured to provide immunity to infants. 
     
     
         23 . The multivalent vaccine composition of  claim 1 , wherein the multivalent vaccine composition is configured to provide immunity to children less than 2 years of age for at least three years. 
     
     
         24 . A method for producing a multivalent vaccine composition comprising Neisseria meningitides serogroups A, C, Y, and W-135 oligosaccharides conjugated to glycan-free carrier proteins, the method comprising:
 non-chemically adjusting sizes of Neisseria meningitides serogroups A, C, Y, and W-135 oligosaccharides;   activating the Neisseria meningitides serogroups A, C, Y, and W-135 oligosaccharides upon non-chemically adjusting the sizes of the Neisseria meningitides serogroups A, C, Y, and W-135 oligosaccharides;   activating glycan-free carrier proteins;   conjugating at least some of the activated Neisseria meningitides serogroups A, C, Y, and W-135 oligosaccharides to at least some of the activated glycan-free carrier proteins; and   producing a multivalent vaccine composition comprising a mixture, the mixture comprising:
 conjugated Neisseria meningitides serogroup A oligosaccharides, each of the conjugated Neisseria meningitides serogroup A oligosaccharides being conjugated to a first particular glycan-free carrier protein of the activated glycan-free carrier proteins; 
 conjugated Neisseria meningitides serogroup C oligosaccharides, each of the conjugated Neisseria meningitides serogroup C oligosaccharides being conjugated to a second particular glycan-free carrier protein of the activated glycan-free carrier proteins; 
 conjugated Neisseria meningitides serogroup Y oligosaccharides, each of the conjugated Neisseria meningitides serogroup Y oligosaccharides being conjugated to a third particular glycan-free carrier protein of the activated glycan-free carrier proteins; and 
 conjugated Neisseria meningitides serogroup W-135 oligosaccharides, each of the conjugated Neisseria meningitides serogroup W-135 oligosaccharides being conjugated to a fourth particular glycan-free carrier protein of the activated glycan-free carrier proteins. 
   
     
     
         25 . The method of  claim 24 , wherein the conjugated A, C, Y, and W-135 oligosaccharides have sizes approximately between 5100 and 9900 Daltons. 
     
     
         26 . The method of  claim 24 , further comprising:
 removing unconjugated oligosaccharides from a mixture including the activated A, C, Y, and W-135 oligosaccharides conjugated to the glycan-free carrier proteins.   
     
     
         27 . The method of  claim 24 , further comprising:
 sterilizing a mixture including the activated A, C, Y, and W-135 oligosaccharides conjugated to the glycan-free carrier proteins.   
     
     
         28 . The method of  claim 24 , further comprising:
 vialing at least a portion of the multivalent vaccine composition comprising Neisseria meningitides serogroups A, C, Y, and W-135 oligosaccharides conjugated to the glycan-free carrier proteins.   
     
     
         29 . The method of  claim 24 , wherein the glycan-free carrier proteins are glycan-free and formalin-free diphtheria toxoid. 
     
     
         30 . The method of  claim 24 , wherein the multivalent vaccine composition is a tetravalent vaccine composition. 
     
     
         31 . The method of  claim 24 , wherein the glycan-free carrier proteins are glycan-free diphtheria toxoid. 
     
     
         32 . An apparatus, comprising:
 a vessel containing a multivalent vaccine composition, the multivalent vaccine composition comprising:
 a mixture comprising:
 conjugated Neisseria meningitides serogroup A oligosaccharides, each of the conjugated Neisseria meningitides serogroup A oligosaccharides being conjugated to a first particular glycan-free carrier protein; 
 conjugated Neisseria meningitides serogroup C oligosaccharides, each of the conjugated Neisseria meningitides serogroup C oligosaccharides being conjugated to a second particular glycan-free carrier protein; 
 conjugated Neisseria meningitides serogroup Y oligosaccharides, each of the conjugated Neisseria meningitides serogroup Y oligosaccharides being conjugated to a third particular glycan-free carrier protein; and 
 conjugated Neisseria meningitides serogroup W-135 oligosaccharides, each of the conjugated Neisseria meningitides serogroup W-135 oligosaccharides being conjugated to a fourth particular glycan-free carrier protein. 
 
   
     
     
         33 . The apparatus of  claim 32 , wherein the vessel is a vial. 
     
     
         34 . A multivalent vaccine composition, comprising: a mixture comprising:
 a plurality of conjugated Neisseria meningitides serogroup oligosaccharides, the plurality of conjugated Neisseria meningitides serogroup oligosaccharides including at least two serogroups of conjugated Neisseria meningitides serogroup A, C, Y, and W-135 oligosaccharides, each of the plurality of conjugated Neisseria meningitides serogroup oligosaccharides being conjugated to a particular glycan-free carrier protein.   
     
     
         35 . The multivalent vaccine composition of  claim 34 , wherein the plurality of conjugated Neisseria meningitides serogroup oligosaccharides including at least three serogroups of conjugated Neisseria meningitides serogroup A, C, Y, and W-135 oligosaccharides. 
     
     
         36 . A vaccine composition, comprising: a mixture comprising:
 conjugated Neisseria meningitides serogroup oligosaccharides, each of the conjugated Neisseria meningitides serogroup oligosaccharides being conjugated to a particular glycan-free carrier protein.