Manufacture of vaccines and compositions for the prevention of Salmonella infections
AssigneeBharat Biotech International Limited
InventorsKrishna Murthy Ella, Venkatesan Ramasamy, Mandalapu Gangadhara Naidu
Life of this patent
Estimating the term…
Abstract
Disclosed are stable conjugate vaccine formulations for protection against Salmonella typhi, and methods of conjugation between Vi-polysaccharide of S. typhi to tetanus toxoid as the carrier protein, responsible for producing improved T-dependent immune response against Typhoid fever caused by Salmonella typhi. The methods disclosed in this invention and the resulting formulations are capable of inducing immunity against typhoid fever including in children below 2 years of age, through only a single injection to comprise a complete vaccination schedule.
Claims30
A method of manufacture of a ViP-carrier protein conjugate comprising:
- purifying capsular Vi-polysaccharide antigens (VIPs) from Salmonella;
- treating the purified VIPs with sodium bicarbonate forming partially de-O-acetylated ViPs;
- treating the partially de-O-acetylated ViPs with a carbodiimide cross-linking agent;
- linking the carbodiimide treated partially de-O-acetylated ViPs with a linker molecule, wherein the linker comprises adipic acid dihydrazide;
- isolating the linked partially de-O-acetylated ViPs;
- and
- contacting the linked partially de-O-acetylated ViPs with a carrier protein in presence of EDAC to form the ViP-carrier protein conjugate.
A method of manufacture of a ViP-carrier protein conjugate comprising:
- treating capsular Vi-polysaccharide antigens (VIPs) of Salmonella typhi with sodium bicarbonate forming partially de-O-acetylated ViPs;
- treating the partially de-O-acetylated ViPs with a carbodiimide cross-linking agent, wherein the cross-linking agent comprises 1-ethyl-3(3-dimethylaminopropyl) carbodiimide (EDAC);
- linking the carbodiimide treated partially de-O-acetylated ViPs with a linker molecule wherein the linker comprises adipic acid dihydrazide;
- isolating the linked partially de-O-acetylated ViPs;
- and
- contacting the linked partially de-O-acetylated ViPs with a carrier protein in presence of EDAC to form the ViP-carrier protein conjugate.
A method of manufacture of an immunogenic composition containing a ViP-carrier protein conjugate comprising:
- treating purifying capsular Vi-polysaccharide antigens (VIPs) of Salmonella typhi with sodium bicarbonate forming partially de-O-acetylated ViPs with a molecular weight of from 250-300 kDa;
- treating the partially de-O-acetylated ViPs with a carbodiimide cross-linking agent;
- linking the carbodiimide treated partially de-O-acetylated ViPs with a linker molecule, wherein the linker molecule comprises adipic acid dihydrazide;
- isolating the linked partially de-O-acetylated ViPs from free linker molecules;
- contacting the linked partially de-O-acetylated ViPs with a carrier protein in presence of EDAC to form the ViP-carrier protein conjugate;
- and
- contacting the ViP-carrier protein conjugate with a preservative, wherein the preservative comprises 2-phenoxy ethanol which is free of mercury chloride and/or thiomersal.
A method of manufacture of a ViP-carrier protein conjugate comprising:
- treating capsular Vi-polysaccharide antigens (VIPs) of Salmonella typhi with sodium bicarbonate forming partially de-O-acetylated ViPs and linking the partially de-O-acetylated ViPs with a linker comprised of adipic acid dihydrazide, wherein the VIP contains no free linker molecules and has an approximate a molecular weight of from 250-300 kDa;
- and
- conjugating the partially de-O-acetylated ViPs with a carrier protein to form the ViP-carrier protein conjugate.
Dependencies are inferred from the claim text.