Bioconjugates made from recombinant N-glycosylated proteins from procaryotic cells

Patent metadata

Field	Value
Publication number	US-11944675-B2
Application number	US-202017061687-A
Country	US
Kind code	B2
Filing date	Oct 2, 2020
Priority date	Feb 20, 2008
Publication date	Apr 2, 2024
Grant date	Apr 2, 2024

Abstract

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.

First claim

The invention claimed is:

1. A bioconjugate vaccine comprising:
(i) a protein carrier, which is a modified, genetically detoxified Exotoxin of Pseudomonas aeruginosa (EPA), comprising at least two[[ ]] inserted consensus sequences, D/E-X-N-Z-S/T, wherein X and Z may be any natural amino acid except proline[[ ]]; and
(ii) at least one antigenic polysaccharide from at least one bacterium, N-linked to the protein carrier by attachment of the antigenic polysaccharide to the asparagine residue of the D/E-X-N-Z-S/T consensus sequence, wherein the at least one antigenic polysaccharide is a bacterial 0-antigen from one or more strain of Shigella, Escherichia coli ( E. coli ) or Pseudomonas aeruginosa ; and,
optionally, an adjuvant.

2. The bioconjugate vaccine of claim 1 , wherein the at least one bacterial O-antigen is from extraintestinal pathogenic E. coli (ExPEC).

3. The bioconjugate vaccine of claim 1 , wherein the modified EPA has a sequence as provided in SEQ ID NO:7.

4. The bioconjugate vaccine of claim 1 , wherein the at least one bacterial O-antigen is from one or more of S. dysenteriae O1, S. flexneri 2a, S. flexneri 3a, S. flexneri 3b, S. flexneri 6 and S. sonnei.

5. The bioconjugate vaccine of claim 1 , wherein the at least one bacterial O-antigen is from Pseudomonas aeruginosa O11.

6. A Shigella bioconjugate vaccine comprising: a protein carrier comprising genetically detoxified Exotoxin of Pseudomonas aeruginosa (EPA) that has been modified to contain at least two consensus sequences D/E-X-N-Z-S/T, wherein X and Z may be any natural amino acid except proline;
at least one polysaccharide chain linked to an asparagine residue of the D/E-X-N-Z-S/T consensus sequence of the protein carrier and having the following structure:

optionally, an adjuvant.

7. The bioconjugate vaccine of claim 1 , wherein the at least one bacterial O-antigen is from one or more of E. coli O4:K52 (ExPEC), E. coli O4:K6 (ExPEC), E. coli O6:K2 (ExPEC); E. coli O6:K54 (ExPEC), E. coli O22 (ExPEC), E. coli O75 (ExPEC), E. coli O83 (ExPEC), E. coli O7, E. coli O9, E. coli O16, E. coli O121 and E. coli O157 (EHEC).

Assignees

• Glaxosmithkline Biologicals Sa

Inventors

• Fernandez Fabiana
• Kowarik Michael
• Wacker Michael
• Wetter Michael

Classifications

• A61K39/0283 Primary

  Shigella · CPC title

• A61K39/0258

  Escherichia · CPC title

• A61K39/104

  {Pseudomonadales, e.g.} Pseudomonas · CPC title

• A61K39/105

  Delta proteobacteriales, e.g. Lawsonia; Epsilon proteobacteriales, e.g. campylobacter, helicobacter · CPC title

• A61K39/385

  Haptens or antigens, bound to carriers · CPC title