Hypo- and hyper-acetylated meningococcal capsular saccharides
AssigneeNovartis AG
InventorsPaolo COSTANTINO, Francesco BERTI
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Abstract
Capsular saccharides derived from serogroups W135 and Y of Neisseria meningitidis have altered levels of O-acetylation at the 7 and 9 positions of their sialic acid residues, and can be used to make immunogenic compositions. Relative to unmodified native saccharides, derivatives of the invention are preferentially selected during conjugation to carrier proteins, and conjugates of the derivatives show improved immunogenicity compared to native polysaccharides.
Claims22
A modified serogroup Y meningococcal capsular saccharide, conjugated to a carrier protein, wherein (a) between 2-9% of the sialic acid residues in the saccharide are O-acetylated at the 7 position;
- and/or (b) between 35-55% of the sialic acid residues in the saccharide are O-acetylated at the 9 position.
A modified meningococcal capsular saccharide conjugated to a carrier protein, wherein the saccharide comprises n or more repeating units of the disaccharide unit:
- [sialic acid]-[hexose]
- wherein n is an integer from 1 to 100, and wherein:
- (a) x % of the sialic acid residues in said n or more repeating units are O-acetylated at the 7 position;
- and/or
- (b) y % of the sialic acid residues in said n or more repeating units are O-acetylated at the 9 position,
- wherein x is between 2-9 and y is between 35-55.
A composition comprising a molecules of serogroup Y meningococcal capsular saccharide, wherein (i) the average number of sialic acid residues per capsular saccharide molecule is b, and wherein:
- (a) between 2-9% of the a·b serogroup Y sialic acid residues in the composition are O-acetylated at the 7 position;
- and/or (b) between 35-55% of the a·b serogroup Y sialic acid residues in the composition are O-acetylated at the 9 position, (ii) the saccharide is conjugated to a carrier protein.
A saccharide comprising n or more repeats of the following disaccharide unit:
- n is an integer from 1 to 100,
- X and Y are different groups selected from —H and —OH,
- R1 is independently selected from —H and —COCH3 and may be the same or different in each disaccharide unit,
- R2 is independently selected from —H and —COCH3 and may be the same or different in each disaccharide unit, and,
- X is —H and Y is —OH, (a) 2-9% of R1 are —COCH3 and/or (b) 35-55% of R2 are —COCH3,
- and wherein the saccharide is conjugated to a carrier protein.
A process for preparing an immunogenic conjugate comprising the steps of:
- (1) providing a starting serogroup Y meningococcal capsular saccharide and a carrier protein, either or both of which is/are optionally modified to render it/them reactive towards the other;
- (2) forming a covalent bond between the saccharide and the carrier protein;
- and (3) purifying the resulting glycoconjugates, wherein, between steps (1) and (3), the degree of O-acetylation at the 9 position of sialic acid residues in the starting saccharide increases to 35-55%.
Dependencies are inferred from the claim text.