Glaxosmithkline Biologicals Sa

Glycovaxyn Ag

Eth Zurich

Oxford University Innovation Limited

Eidgenossische Technische Hochschule Zurich

Michael Wacker

Michael T Kowarik

Michael L Wetter

Amirreza Faridmoayer

Markus Aebi

Benjamin G Davis

Fabiana Fernandez

Charles Waechter

Balakumar Vijayakrishnan

Feng Lui

Michael Thomas Kowarik

Described herein are methods of inserting nucleic acid sequences into host cells. Also described herein are genetically stable host cells comprising inserted nucleic acid sequences and methods of using such host cells in the generation of proteins.

Methods of host cell modification

The present invention is directed to a bioconjugate vaccine, such as an O 1-bioconjugate vaccine, comprising: a protein carrier comprising a protein carrier containing at least one consensus sequence, DIE-X-N-Z-S/T, wherein X and Z may be any natural amino acid except proline; at least one antigenic polysaccharide from at least one pathogenic bacterium, linked to the protein carrier; and, optionally, an adjuvant. In another aspect, the present invention is directed to a method of producing an O 1-bioconjugate in a bioreactor comprising a number steps.

Bioconjugates made from recombinant N-glycosylated proteins from procaryotic cells

Provided herein are prokaryotic cells proficient to produce glycoconjugates in vivo, as well as methods for generating these cell and methods of using these cells to produce glycoconjugates. The compositions of the mentioned glycoconjugates as well as their different uses are also included.

Production of recombinant vaccine inby enzymatic conjugation

The present invention is directed to a bioconjugate vaccine, such as an O1-bioconjugate vaccine, comprising: a protein carrier comprising a protein carrier containing at least one consensus sequence, D/E-X-N-Z-S/T, wherein X and Z may be any natural amino acid except proline; at least one antigenic polysaccharide from at least one pathogenic bacterium, linked to the protein carrier; and, optionally, an adjuvant. In another aspect, the present invention is directed to a method of producing an O1-bioconjugate in a bioreactor comprising a number steps.

The present invention encompasses a novelbioconjugate vaccine. More generally, the invention is directed to Gram-positive and other bioconjugate vaccines containing a protein carrier, at least one polysaccharide such as a capsular Gram-positive polysaccharide, and, optionally, an adjuvant or pharmaceutically acceptable carrier. The instant invention also includes methods of producing Gram-positive and other bioconjugate vaccines. An N-glycosylated protein is also provided that contains one or more polysaccharides such as Gram-positive polysaccharides. The invention is additionally directed to engineered prokaryotic organisms comprising nucleotide sequences encoding a glycosyltransferase of a first prokaryotic organism and a glycosyltransferase of a second prokaryotic organism. The invention further includes plasmids and prokaryotic cells transformed with plasmids encoding polysaccharides and enzymes which produce an N-glycosylated protein and/or bioconjugate vaccine. Further, the invention is directed to methods of inducing an immune response in a mammal comprising administering said bioconjugate vaccines.

Capsular gram-positive bacteria bioconjugate vaccines

Provided herein are immunogenic compositions and vaccines for the treatment and prevention ofinfections. These immunogenic compositions and vaccines comprise combinations of bioconjugates capsular polysaccharides that are N-linked to one or more carrier proteins.

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The invention is directed to bioconjugate vaccines comprising N-glycosylated proteins. Further, the present invention is directed to a recombinant prokaryotic biosynthetic system comprising nucleic acids encoding an epimerase that synthesizes an oligo- or polysaccharide having N-acetylgalactosamine at the reducing terminus. The invention is further directed to N-glycosylated proteins containing an oligo- or polysaccharide having N-acetylgalactosamine at the reducing terminus and an expression system and methods for producing such N-glycosylated proteins.

Biosynthetic system that produces immunogenic polysaccharides in prokaryotic cells

A system and a method for the production of recombinant N-glycosylated target proteins. The system comprises a prokaryotic organism (e.g.) into which is introduced a genetic information encoding for a metabolic apparatus capable of carrying out the requested N-glycosylation of the target protein. Said prokaryotic organism also contains the genetic information required for the expression of one or more recombinant target proteins. The metabolic apparatus preferably comprises specific glycosyltransferases for the assembly of the oligosaccharide on a lipid carrier and an OTase that covalently links this oligosaccharide to specific residues of the desired protein.

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Unterengstringen, Switzerland

Michael Wacker