Methods for the prevention of Salmonella infections
Inventors
Ella, Krishna Murthy • Ramasamy, Venkatesan • Naidu, Mandalapu Gangadhara
Assignees
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Publication Number
US-10758604-B2
Publication Date
2020-09-01
Expiration Date
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.
Core Innovation
The invention provides vaccine compositions comprising a compound of partially de-O-acetylated capsular Vi-polysaccharide of Salmonella coupled to a linker molecule that comprises adipic acid dihydrazide, where the compound is conjugated to a carrier protein and wherein no free linker molecules are coupled to the carrier protein. The compositions are configured to elicit a T-dependent immune response against typhoid fever caused by Salmonella in a subject upon administration.
The immunogenic compound includes partially de-O-acetylated capsular Vi-polysaccharide antigen of Salmonella and constrains the antigen molecular weight to be from 250 to 300 kDa, or less than 1,000 kDa in another embodiment. The linker coupling is limited to the antigen, and coupling of linker molecules to the carrier protein is constrained by requiring no free linker molecules coupled to the carrier protein.
The invention further specifies prophylaxis and treatment use through administration of these compositions, including dosing of 15-25 μg of the compound per 0.5 ml of immunogenic composition. The document also describes formulation features such as 2 phenoxy-ethanol as a preservative in specified embodiments, and immune performance criteria including seroconversion and a four-fold increase on the 42nd day post administration.
Claims Coverage
The independent claims cover four related methods and compositions centered on a Vi-polysaccharide conjugate vaccine for typhoid fever caused by Salmonella. The claims consistently require a partially de-O-acetylated capsular Vi-polysaccharide coupled via an adipic acid dihydrazide-containing linker to a carrier protein with no free linker molecules coupled to the carrier protein, and they add molecular-weight, dosing, prophylaxis, treatment, and preservative limitations.
Partially de-o-acetylated Vi-polysaccharide conjugate with no free linker
providing a vaccine composition comprising a compound of partially de-O-acetylated capsular Vi-polysaccharide of Salmonella coupled to a linker molecule that comprises adipic acid dihydrazide, which is conjugated to a carrier protein, wherein no free linker molecules are coupled to the carrier protein
Administration that elicits a T-dependent immune response against typhoid fever
administering the vaccine composition to the subject, which elicits the T-dependent immune response against typhoid fever caused by Salmonella
Prophylaxis via T-dependent immune response using less than 1,000 kDa conjugate
providing a vaccine composition comprising a compound of partially de-O-acetylated capsular Vi-polysaccharide of Salmonella coupled to a linker molecule that comprises adipic acid dihydrazide, which is conjugated to a carrier protein, wherein no free linker molecules are coupled to the carrier protein and the compound has an approximate molecular weight of less than 1,000 kDa
Treatment with immunogenic composition constrained to 250-300 kDa antigen
providing an immunogenic composition comprising a partially de-O-acetylated capsular Vi-polysaccharide antigen of Salmonella coupled to a linker molecule, wherein the linker molecule comprises adipic acid dihydrazide, which is conjugated to a carrier protein, wherein no free linker molecules are coupled to the carrier protein and coupling of linker molecules is limited to the antigen and the molecular weight of the antigen is from 250 to 300 kDa
Dose of 15-25 μg per 0.5 ml for immunogenic composition
administering the immunogenic composition to the patient at a dose of from 15-25 μg of the compound per 0.5 ml of the immunogenic composition
Prophylaxis with preservative-containing immunogenic composition
providing an immunogenic composition comprising a partially de-O-acetylated capsular Vi-polysaccharide antigen of Salmonella coupled to a linker molecule that comprises adipic acid dihydrazide, which is conjugated to a carrier protein, wherein no free linker molecules are coupled to the carrier protein and the molecular weight of the antigen is from 250 to 300 kDa and the immunogenic composition contains 2 phenoxy-ethanol as a preservative
The independent claim set is directed to prophylaxis and treatment methods based on administering a conjugate built from partially de-O-acetylated capsular Vi-polysaccharide of Salmonella linked via an adipic acid dihydrazide-containing linker to a carrier protein, explicitly requiring no free linker coupled to the carrier protein. The coverage further distinguishes embodiments by antigen molecular-weight constraints, administration dose normalized to 0.5 ml, and inclusion of 2 phenoxy-ethanol as a preservative.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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