Multivalent conjugate vaccines with bivalent or multivalent conjugate polysaccharides that provide improved immunogenicity and avidity
Inventors
Kapre, Subhash V. • Datta, Anup K.
Assignees
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Publication Number
US-10688170-B2
Publication Date
2020-06-23
Expiration Date
Abstract
The disclosure describes compositions containing conjugates using novel linkers, bivalent polysaccharide conjugates, and methods of bivalent polysaccharide conjugation in the development of multivalent conjugate vaccines. Conjugation of capsular polysaccharides to carrier proteins is carried out using homo-bifunctional and/or hetero-bifunctional linkers of specific lengths. Incorporation of the linkers and their use in bifunctional linkers induces higher titers of functional antibodies with high avidity, eliciting higher immunologic memory, and reduced carrier protein effect. This provides immunochemically cross-reactive capsular polysaccharides wherein one or more cross-reactive capsular polysaccharides are conjugated sequentially or concurrently to carrier protein using bifunctional linkers bearing the same or different functional groups. Such a linker and the size of the capsular polysaccharides provides an effective multivalent conjugate vaccine with high antibody titers and a reduced carrier effect and results in reduction in the content of the capsular polysaccharide and protein per dose of vaccine which reduces reactogenicity.
Core Innovation
The immunogenic composition combines a first collection of monovalent conjugates containing capsular polysaccharides of Streptococcus pneumoniae serotypes 1, 2, 3, 4, 5, 7F, 8, 10A, 11A, 12F, 14, 17F, 18C, 20, 22F, 23F, 24F, 33F, and 35B with a second collection of bivalent or multivalent conjugates. The latter conjugates contain polysaccharides from specified groups of cross-reactive serotypes and use a second carrier protein.
One or more polysaccharides in the bivalent or multivalent conjugates are coupled via a bifunctional linker, and the multivalent conjugate contains less carrier protein than capsular polysaccharide. The disclosure reports improved polysaccharide-specific IgG responses for long-linker and bivalent formulations, reduced carrier-protein content, and retained polysaccharide structural integrity for serotypes 6A/6B.
Claims Coverage
The supplied relevant claims identify one independent claim, claim 1, which covers an immunogenic composition through three inventive features.
First collection of monovalent conjugates
The first group conjugates comprise a first collection of monovalent conjugates, each comprising a first carrier protein and a capsular polysaccharide of Streptococcus pneumoniae. The collection includes serotypes 1, 2, 3, 4, 5, 7F, 8, 10A, 11A, 12F, 14, 17F, 18C, 20, 22F, 23F, 24F, 33F, and 35B.
Second collection of bivalent and multivalent conjugates
The second group conjugates comprise a second collection of bivalent and/or multivalent conjugates, each comprising a second carrier protein and at least two capsular polysaccharides of Streptococcus pneumoniae selected from the specified groups of serotypes 6A, 6B, 6C, and 6D; 9V, 9N, 9A, and 9B; 15B, 15A, and 15C; and 19A and 19F.
Bifunctional linker and carrier-protein quantity
One or more of the capsular polysaccharides are coupled via a bifunctional linker, and the multivalent conjugate contains a quantity of carrier protein that is less than a quantity of capsular polysaccharide.
Claim 1 covers a composition combining specified monovalent conjugates with bivalent and/or multivalent conjugates from specified serotype groups, with a bifunctional linker and less carrier protein than capsular polysaccharide in the multivalent conjugate.
Stated Advantages
Improved polysaccharide-specific IgG responses for long-linker and bivalent formulations.
Reduced carrier-protein content in reported formulations.
Retained polysaccharide structural integrity for serotypes 6A/6B as indicated by NMR spectra.
Documented Applications
Not explicitly described in patent.
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