Immunogenic composition having improved stability, enhanced immunogenicity and reduced reactogenicity and process for preparation thereof
Inventors
Kumar, Rakesh • SHARMA, Inder Jit • SHITOLE, Anil Vyankatrao • DODDAPANENI, Manohar • SHARMA, Hitt Jyoti
Assignees
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Publication Number
US-11179453-B2
Publication Date
2021-11-23
Expiration Date
Abstract
An immunogenic composition comprising of Diphtheria toxoid antigen (D), tetanus toxoid (T) antigen, Hepatitis B surface antigen (HBsAg), inactivated whole-cell B. pertussis (wP) antigen, Haemophilus influenzae type B (Hib) capsular saccharide conjugated to a carrier protein, Inactivated Polio Virus (IPV) antigen and additionally one or more antigens and the method of preparing the same. A fully liquid combination vaccine, showing improved immunogenicity, reduced reactogenicity and improved stability. Improved methods of formaldehyde inactivation, improved adsorption profile of Diphtheria toxoid antigen (D), tetanus toxoid (T) antigen and Hepatitis B (HepB) surface antigen adsorbed individually onto aluminium phosphate adjuvant, minimum total aluminum content (Al3+) and optimized concentration of 2-phenoxyethanol (2-PE) as preservative.
Core Innovation
The invention provides a fully liquid combination vaccine immunogenic composition in which a single per-dose amount includes diphtheria toxoid (D), tetanus toxoid (T), inactivated whole-cell pertussis antigen (wP), hepatitis B virus surface antigen (HBsAg), Haemophilus influenzae type b (Hib) capsular saccharide conjugated to Tetanus Toxoid as carrier protein, and inactivated polio virus antigen (IPV). The composition is defined so that each component has specified ranges and, for multiple antigens, specified percentage adsorption onto an aluminum salt, together with defined total aluminum content (Al3+), preservative level, and a dilution medium including NaCl.
A further core aspect is that the wP antigen contains inactivated Bordetella pertussis strains 134, 509, 25525 and 6229 in a defined strain ratio (1:1:0.25:0.25) with a specified amount expressed as IOU. The composition also defines the IPV antigen by specifying type 1, type 2, and type 3 in separate dose ranges in DU and, in refinement embodiments, restricts the IPV antigens to selected Salk strains and/or Sabin strains by type.
In refinement embodiments, the Hib capsular saccharide conjugation to Tetanus Toxoid is further characterized by specifying Hib PRP conjugation to a carrier protein via a cyanylation or reductive amination conjugation chemistry, including enumeration of particular cyanylation reagents. Additional refinements also address adsorption behavior for particular antigens relative to adjuvant, and define quantitative constraints for embodiments of the fully liquid combination vaccine.
Claims Coverage
The independent claim covers an immunogenic fully liquid combination vaccine composition with multiple specified antigen classes (D, T, wP, HBsAg, Hib conjugate, IPV) plus defined aluminum (as aluminum phosphate), preservative, and NaCl buffer, and specifies inventive feature constraints including adsorption percentages and defined per-dose ranges. Independent claim coverage is concentrated in one independent claim (clm-00001).
Fully liquid combination vaccine composition with defined multi-antigen dose ranges
An immunogenic composition wherein 0.5 ml comprises diphtheria toxoid (D), tetanus toxoid (T), inactivated whole cell pertussis antigen (wP) containing inactivated Bordetella pertussis strains 134, 509, 25525 and 6229 in a ratio of 1:1:0.25:0.25, hepatitis B virus surface antigen (HBsAg), Hib capsular saccharide conjugated to Tetanus Toxoid as carrier protein, and an inactivated polio virus antigen (IPV) of types 1, 2 and 3, together with total aluminum content (Al3+) as aluminum phosphate adjuvant, 2-phenoxyethanol preservative, and a dilution medium or buffer including NaCl; wherein the composition is a fully liquid combination vaccine.
Adsorption-defined aluminum salt binding for D, T, and HBsAg
D in a range of 10 Lf to 25 Lf adsorbed onto aluminum salt having percentage adsorption of at least 50%; T in a range of 2 Lf to 10 Lf adsorbed onto the aluminum salt having percentage adsorption of at least 40%; and HBsAg in a range of 7 µg to 15 µg adsorbed onto the aluminum salt having percentage adsorption of at least 70%.
Defined wP strain composition and wP antigen dose range
wP containing inactivated Bordetella pertussis strains 134, 509, 25525 and 6229 in a ratio of 1:1:0.25:0.25, in a range of 12 IOU to 16 IOU.
Hib PRP conjugate to tetanus toxoid and specified Hib dose range
Hib capsular saccharide conjugated to Tetanus Toxoid as a carrier protein, in a range of 7 µg to 13 µg.
IPV antigen type-specific dose ranges
An inactivated polio virus antigen containing IPV antigen type 1 in a range of 1-50 DU, Type 2 in a range of 1-20 DU or type 3 in a range of 1-50 DU, respectively.
Defined total aluminum, preservative, and NaCl dilution medium
total aluminum content (Al3+) as aluminum phosphate adjuvant in a range of 0.1 mg to 0.5 mg; 2-phenoxyethanol as a preservative in a range of 1 mg to 3 mg; and as a dilution medium or buffer including a range of 0.5% to 1.5% NaCl.
Overall, the claim coverage centers on a fully liquid combination vaccine that integrates defined antigen classes with explicit adsorption percentage constraints for D, T, and HBsAg, a defined wP Bordetella pertussis strain ratio and IOU range, defined dose ranges for Hib and type-specific IPV DU ranges, and defined formulation levels for aluminum phosphate adjuvant (total Al3+), 2-phenoxyethanol preservative, and NaCl dilution medium. Refinement claims further restrict or specify IPV strain sets, Hib conjugation chemistry, and certain adsorption conditions for selected antigens.
Stated Advantages
Improved immunogenicity, stability, and reduced reactogenicity.
Documented Applications
No documented applications found
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