Abstract: A process is provided for preparing a conjugate of Formula (I-A) or (I) comprising a polypeptide containing n number of tyrosine units, where n is an integer greater than or equal to 1, dispersed within the amino acid chain having and amino terminus end (A1) and an acid terminus end (A2) of the protein or polypeptide and having a weight average molecular weight equal to or greater than 10,000 Daltons (10 kDa), wherein the conjugate comprises a number m of tyrosine conjugates (modified tyrosine residues) as depicted in Formula (I-A) or (I), where m is at least one and is less than or equal to n: where X, Lg, L and R are as defined herein.

Abstract: This invention is in the field of bacterial cultures and specifically relates to the optimization of culture conditions to improve the production of bacterial capsular polysaccharides from Streptococcus strains in fed batch culture and to novel purification methods suitable for production scale purification of bacterial capsular polysaccharides from Streptococcus strains resulting in higher levels of purity than previously obtained for production scale.

Abstract: Glucans having exclusively or mainly ?-1,3 linkages are used as immunogens. These comprise ?-1,3-linked glucose residues. Optionally, they may include ?-1,6-linked glucose residues, provided that the ratio of ?-1,3-linked residues to ?-1,6-linked residues is at least 8:1 and/or there are one or more sequences of at least five adjacent non-terminal residues linked to other residues only by ?-1,3 linkages. The glucans will usually be used in conjugated form. A preferred glucan source is curdlan, which may be hydrolysed to a suitable form prior to conjugation.

Abstract: The invention provides a synthetic C. difficile PS-II cell wall saccharide. The invention also provides a process for purifying C. difficile PS-II saccharide from C. difficile bacterial cells resulting in reduced contamination. The saccharides may be used in vaccines, particularly as conjugates with carrier proteins.

Abstract: Three conjugation methods for use with the capsular saccharide of Streptococcus agalactiae. In the first method, reductive animation of oxidised sialic acid residue side chains is used, but the aldehyde groups are first aminated, and then the amine is coupled to a carrier via a linker. In the second method, sialic acid residues and/or N-acetyl-glucosamine residues are de-N-acetylated to give amine groups, and the amine groups are coupled to a carrier protein via a linker. In the third method, linkage is via galactose residues in the capsular saccharide rather than sialic acid residues, which can conveniently be achieved using galactose oxidase.

Abstract: The invention provides an immunogenic composition comprising: a) a conjugate that is a capsular saccharide from GBS serotype 1a conjugated to a carrier protein; b) a conjugate that is a capsular saccharide from GBS serotype 1b conjugated to a carrier protein; and c) a conjugate that is a capsular saccharide from GBS serotype III conjugated to a carrier protein. The invention also provides a method for immunising a patient against infection by GBS comprising the step of administering to the patient a conjugate that is a capsular saccharide from GBS conjugated to a diphtheria toxoid or derivative thereof, wherein the patient has been pre-immunised with a diphtheria toxoid or derivative thereof.

Abstract: Three conjugation methods for use with the capsular saccharide of Streptococcus agalactiae. In the first method, reductive animation of oxidized sialic acid residue side chains is used, but the aldehyde groups are first aminated, and then the amine is coupled to a carrier via a linker. In the second method, sialic acid residues and/or N-acetyl-glucosamine residues are de-N-acetylated to give amine groups, and the amine groups are coupled to a carrier protein via a linker. In the third method, linkage is via galactose residues in the capsular saccharide rather than sialic acid residues, which can conveniently be achieved using galactose oxidase.

Abstract: This invention is in the field of bacterial cultures and specifically relates to the optimization of culture conditions to improve the production of bacterial capsular polysaccharides from Streptococcus strains in fed batch culture and to novel purification methods suitable for production scale purification of bacterial capsular polysaccharides from Streptococcus strains resulting in higher levels of purity than previously obtained for production scale.

Abstract: E. coli proteins have been identified that are useful as carrier proteins to improve a response to a polysaccharide immunogen conjugated to such protein. In particular, AcfD precursor protein (orf3526 polypeptide), Flu antigen 43 protein (orf1364 polypeptide), and Sel1 repeat-containing protein (upec-5211 polypeptide) have been shown to be effective. Additionally, these E. coli proteins can enhance the immune response to glucans, particularly fungal glucans.

Abstract: The invention provides a method for releasing capsular polysaccharide from S. aureus type 5 or type 8 cells, comprising the step of treating the cells with acid. The invention further provides a process for purifying capsular polysaccharide from S. aureus type 5 or type 8 cells comprising this method. Other processing steps may be included in the process, such as enzymatic treatment, e.g. to remove nucleic acid, protein and/or peptidoglycan contaminants; diafiltration, e.g. to remove low molecular weight contaminants; anion exchange chromatography, e.g. to remove residual protein; and concentration.

Abstract: The invention provides a process for preparing a conjugate of a S. aurens type 5 or type 8 capsular polysaccharide and a carrier molecule, comprising the steps of: (a) depolymerising the capsular polysaccharide, to give a polysaccharide fragment; (b) oxidising the fragment in order to introduce an aldehyde group into at least one saccharide residue in the fragment, to give an oxidised saccharide residue; and (c) coupling the oxidised saccharide residue to a carrier molecule via the aldehyde group, thereby giving the conjugate. The coupling in step (c) may be direct, or may be via a linker molecule. The invention also provides a conjugate obtained or obtainable by this process.

Abstract: A process for purifying a Streptococcus pyogenes GAS carbohydrate comprising a step of anionic exchange chromatography. The process provides a good yield of GAS carbohydrate. The saccharides of the invention have low levels of hyaluronic acid, protein and nucleic acid contamination.

Abstract: Salmonella typhi Vi saccharide can be assayed in two new ways. First, its proton NMR spectrum can be used, with comparison to an internal Standard permitting quantitative analysis. Second, anion exchange chromatography with amperometric detection can be used on hydrolysed saccharide.

Abstract: Two Vi conjugates have been prepared by carbodiimide-mediated synthesis, using adipic acid dihydrazide derivatized CRM197 (a non-toxic variant of diphtheria toxin) and tetanus toxoid, as carrier proteins.

Abstract: Glucans having exclusively or mainly ?-1,3 linkages are used as immunogens. These comprise ?-1,3-linked glucose residues. Optionally, they may include ?-1,6-linked glucose residues, provided that the ratio of ?-1,3-linked residues to ?-1,6-linked residues is at least 8:1 and/or there are one or more sequences of at least five adjacent non-terminal residues linked to other residues only by ?-1,3 linkages. The glucans will usually be used in conjugated form. A preferred glucan source is curdlan, which may be hydrolysed to a suitable form prior to conjugation.

Abstract: Modified capsular saccharides comprising a blocking group at a hydroxyl group position on at least one of the monosaccharide units of the corresponding native capsular saccharide, wherein the blocking group is of the formula (Ia) or (Ib): —OX—Y (Ia) or —O—R1 (Ib) wherein X is C(O), S(O) or SO2; Y is NR1R2 or R3; R1 is C1-6 alkyl substituted with 1, 2 or 3 groups independently selected from hydroxyl, sulphydryl and amine; R2 is H or C1-6 alkyl; and R3 is C1-6 alkyl; processes for modifying a capsular saccharide with the blocking groups; saccharide-protein conjugates comprising the modified capsular saccharide; processes for making the saccharide-protein conjugates, pharmaceutical compositions comprising the modified capsular saccharides and/or saccharide-protein conjugates; and methods and uses of the same.

Abstract: This invention is in the field of bacterial cultures and specifically relates to the optimization of culture conditions to improve the production of bacterial capsular polysaccharides from Streptococcus strains in fed batch culture and to novel purification methods suitable for production scale purification of bacterial capsular polysaccharides from Streptococcus strains resulting in higher levels of purity than previously obtained for production scale.

Abstract: The use of beta-glucans as antigens for immunising against fungi is known. According to the invention, the beta-glucans are administered together with an adjuvant. The adjuvant improves the immune response. The glucan will usually be conjugated to a carrier. Suitable glucans include laminarin and curdlan.

Abstract: This application relates to methods for the purification of saccharide antigen-carrier protein conjugates. In particular, the invention provides a method for purifying saccharide antigen- carrier protein conjugates from free carrier protein, such as CRM1 97, using hydroxyapatite. The invention further relates to methods of preparing vaccines, using this method.

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 unmodifed 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.