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 efficacy of S. pneumoniae vaccines can be enhanced by adjuvanting S. pneumoniae saccharide and/or protein antigens with a mixture of a TLR agonist (preferably a TLR7 agonist) and an insoluble metal salt (preferably an aluminium salt). The TLR agonist is typically adsorbed to the metal salt. The S. pneumoniae antigen can also be adsorbed to the metal salt.

Abstract: The invention provides a conjugate of a Neisseria meningitidis serogroup X capsular polysaccharide and a carrier molecule. The conjugate is typically made by (a) oxidising a primary hydroxyl group in the capsular polysaccharide, to give an oxidised polysaccharide with an aldehyde group; and (b) coupling the oxidised polysaccharide to a carrier molecule via the aldehyde group, thereby giving the conjugate. The conjugate may be part of an immunogenic composition. This composition may comprise one or more further antigens, particularly capsular polysaccharides from serogroups A, W135, C and Y and conjugated forms thereof. The composition may be in an aqueous formulation. The composition is useful as a vaccine, e.g. for raising an immune response in a mammal. The invention also provides processes for making the conjugate.

Abstract: The invention provides a process for preparing a conjugate of a S. aureus type 5 or type 8 capsular polysaccharide and a carrier molecule, comprising the steps of: (a) depolymerizing the capsular polysaccharide, to give a polysaccharide fragment; (b) oxidizing the fragment in order to introduce an aldehyde group into at least one saccharide residue in the fragment, to give an oxidized saccharide residue; and (c) coupling the oxidized 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: Saccharide-protein conjugates having a new type of linker are described. The conjugates comprising the new linker are prepared from modified saccharides comprising a moiety of the formula (I): -A-N(R1)-L-M wherein: A is a bond, —C(O)— or —OC(O)—; R1 is selected from H or C1-C6 alkyl; L is a C1-C12 alkylene group; and M is a masked aldehyde group. The new linker is especially useful for preparing conjugates of Neisseria meningitidis serogroup A saccharide. Conjugates having this new linker have improved immunogenicity compared to other types of conjugates.

Abstract: Precipitated bacterial capsular polysaccharides can be efficiently re-solubilized using alcohols as solvents. The invention provides a process for purifying a bacterial capsular polysaccharide, comprising the steps of (a) precipitation of said polysaccharide, followed by (b) solubilization of the precipitated polysaccharide using ethanol. CTAB can be used for step (a). The material obtained, preferably following hydrolysis and sizing, can be conjugated to a carrier protein and formulated as a vaccine. Also, in vaccines comprising saccharides from both serogroups A and C, the invention provides that the ratio (w/w) of MenA saccharide:MenC saccharide is >1.

Abstract: Precipitated bacterial capsular polysaccharides can be efficiently re-solubilized using alcohols as solvents. The invention provides a process for purifying a bacterial capsular polysaccharide, comprising the steps of (a) precipitation of said polysaccharide, followed by (b) solubilization of the precipitated polysaccharide using ethanol. CTAB can be used for step (a). The material obtained, preferably following hydrolysis and sizing, can be conjugated to a carrier protein and formulated as a vaccine. Also, in vaccines comprising saccharides from both serogroups A and C, the invention provides that the ratio (w/w) of MenA saccharide:MenC saccharide is >1.

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.

Abstract: Precipitated bacterial capsular polysaccharides can be efficiently re-solubilized using alcohols as solvents. The invention provides a process for purifying a bacterial capsular polysaccharide, comprising the steps of (a) precipitation of said polysaccharide, followed by (b) solubilization of the precipitated polysaccharide using ethanol. CTAB can be used for step (a). The material obtained, preferably following hydrolysis and sizing, can be conjugated to a carrier protein and formulated as a vaccine. Also, in vaccines comprising saccharides from the serogroups A and C, the invention provides that the ratio (w/w) of MenA saccharide:MenC saccharide is >1.

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: 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: 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: Meningococcal lipooligosaccharide and pneumococcal serotype 14 capsular saccharide share an antigen that can cross-react with human tissue. The invention provides various ways of minimising the production of autoreactive antibodies when these two antigens are co-administered.

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: An oligosaccharide useful for a Meningitidis A vaccine contains a first mannose unit having a spacer in the alpha configuration at C-1, which spacer is capable of conjugating to a protein, and which is connected to a second mannose unit through a 1,6-linkage which connects C-6 of the first unit to C-1 of the second unit, wherein the 1,6-linkage comprises a phosphonate. Related methods of making such compounds, analogous compounds, or intermediates thereof are also disclosed.