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: 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-solubilised 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) solubilisation 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 Men A saccharide: MenC saccharide is >1.

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: An injectable immunogenic composition comprising capsular saccharides from at least two of serogroups A, C, W135 and Y of Neisseria meningitidis, wherein said capsular saccharides are conjugated to carrier protein(s) and/or are oligosaccharides, and wherein (i) the composition comprises <50 ?g meningococcal saccharide per dose, and/or (ii) the composition further comprises an antigen from one or more of (a) serogroup B N. meningitidis; (b) Haemophilus influenzae type B; and/or (c) Streptococcus pneumoniae. Saccharide antigens in the compositions are generally conjugated to a carrier.

Abstract: The invention provides a conjugate comprising an antigen and a carrier molecule, wherein the carrier molecule comprises a spr0096 antigen and a spr2021 antigen. spr0096 and spr2021 are Streptococcus pneumoniae antigens. The conjugate may be used in a method for raising an immune response in a mammal, the method comprising administering the conjugate to the mammal. Also provided are pharmaceutical compositions, particularly vaccines, comprising the conjugate.

Abstract: Carrier-induced epitopic suppression is of particular concern where multiple conjugates with the same carrier protein are administered simultaneously. To avoid the suppression, the invention minimizes the amount of unconjugated carrier protein in a vaccine. The invention provides a composition for immunizing a patient against a disease caused by Neisseria meningitidis, wherein (1) the composition comprises conjugates for at least two of the four meningococcal serogroups A, C, W135 and Y, where at least two of the conjugates have a common carrier protein; and (2) the composition includes the common carrier in an unconjugated form at less than 10 ?g/ml.

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: Precipitated bacterial capsular polysaccharides can be efficiently re-solubilised 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) solubilisation 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: 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 hydrolyzed to a suitable form prior to conjugation.

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 hydrolyzed to a suitable form prior to conjugation.

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: Precipitated bacterial capsular polysaccharides can be efficiently re-solubilised 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) solubilisation 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: 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: This specification is directed to nonlinear saccharide conjugates that comprise polysaccharides that are linked to at least two peptides that comprise T-cell epitopes and have no conformational B-cell epitopes where one of the peptides is linked to an internal saccharide so that the conjugates have a branched (i.e., nonlinear) structure. The specification also provides methods of manufacturing these conjugates, methods of formulating these conjugates in compositions for use as vaccines and methods of using the compositions to induce an immune response to the capsular saccharide. The specification also provides a new polyepitope carrier peptide comprising the PV1 epitope from polio virus. The new polyepitope carrier peptide can be used in both linear saccharide conjugates as well as the nonlinear saccharide conjugates.

Abstract: The invention provides a process for preparing a conjugate of a S. aureus 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: 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 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: 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 an immunogenic composition comprising: (a) a conjugate that is a capsular saccharide from GBS serotype I1 conjugated to a carrier protein; (b) a conjugate that is a capsular saccharide from GBS serotype Ib 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 immunizing 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-immunized with a diphtheria toxoid or derivative thereof.