Glaxosmithkline Biologicals Sa

Novartis Ag

Francesca Micoli

Allan James Saul

Paolo Costantino

Francesco Berti

Maria Rosaria Romano

Roberto Adamo

Renzo Alfini

Laura Serino

Laura Bartle Martin

Anna Kabanova

Marta Tontini

Roberta Di Benedetto

Calman Alexander MacLennan

Calman Alexander Maclennan

The provided technology is in the field of conjugating native, non-detergent extracted, outer membrane vesicles (nOMV) to antigens to form nOMV-antigen conjugates, which are particularly useful for immunogenic compositions and immunisation; processes for the preparation and use of such conjugates is also provided.

Immunogenic conjugates and use thereof

The present invention is in the field of conjugating native, non-detergent extracted, outer membrane vesicles (nOMV) to multiple antigens to form multi functionalized nOMV-antigen conjugated derivatives, which are particularly useful for immunogenic compositions and immunisation; processes for the preparation and use of such conjugates are also provided.

Multi-functionalized nOMV conjugates

The invention provides a process for the reductive amination of a carbonyl group at the reducing terminus of a polysaccharide, wherein the reductive amination is carried out at a pH between 4 and 5. The invention also provides a process for preparing a conjugate of a polysaccharide and a carrier molecule, comprising the steps of: (a) coupling the polysaccharide to a linker, to form a polysaccharide-linker compound in which the free terminus of the linker is an ester group; and (b) reacting the ester group with a primary amine group in the carrier molecule, to form a polysaccharide-linker-carrier molecule conjugate in which the linker is coupled to the carrier molecule via an amide linkage. The invention also provides a process for reducing contamination of a polysaccharide-linker compound with unreacted linker, comprising a step of precipitating unreacted linker under aqueous conditions at a pH of less than 5. The invention also provides polysaccharide-linker-carrier molecule conjugates and intermediate compounds obtained or obtainable by these processes.

Methods for making saccharide-protein glycoconjugates

The invention provides a conjugate of aserogroup 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.

Meningococcus serogroup X conjugate

The invention provides a conjugate of aserogroup X capsular polysaccharide and a carrier molecule. The conjugate is typically made by (a) oxidizing a primary hydroxyl group in the capsular polysaccharide, to give an oxidized polysaccharide with an aldehyde group; and (b) coupling the oxidized 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.

The invention relates to a conjugate based on Vi polysaccharide which is fragmented and a carrier protein, to compositions comprising said conjugate and to methods for making said conjugates and compositions.

Salmonella conjugate vaccines

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

Conjugated Vi saccharides

The invention provides a process for the reductive amination of a carbonyl group at the reducing terminus of a polysaccharide, wherein the reductive amination is carried out at a pH between 4 and 5. The invention also provides a process for preparing a conjugate of a polysaccharide and a carrier molecule, comprising the steps of: (a) coupling the polysaccharide to a linker, to form a polysaccharide-linker compound in which the free terminus of the linker is an ester group; and (b) reacting the ester group with a primary amine group in the carrier molecule, to form a polysaccharide-linker-carrier molecule conjugate in which the linker is coupled to the carrier molecule via an amide linkage. The invention also provides a process for reducing contamination of a polysaccharide-linker compound with unreacted linker, comprising a step of precipitating unreacted linker under aqueous conditions at a pH of less than 5.

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, theseproteins can enhance the immune response to glucans, particularly fungal glucans.

Growing community of inventors

Florence, Italy

Francesca Micoli