IP Library Granted Patent US 11,339,367
Granted Patent B2
US 11,339,367 · App. 15/094,077 · Granted May 24, 2022

Hyperblebbing

Inventors: Christiane Gerke (Siena, IT); Francesco Berlanda Scorza (Siena, IT); Allan Saul (Siena, IT); Luana Maggiore (Siena, IT)
Assignee: GLAXOSMITHKLINE BIOLOGICALS SA
C12N1/20C07K14/25A61K39/00A61K2035/122Y02A50/30
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Quick Facts
Patent No.
US 11,339,367
App. No.
15/094,077
Granted
May 24, 2022
Kind
B2
Abstract

Hyperblebbing Shigella strains are generated by disrupting one or more components of the Tol-Pal system. The blebs from these strains are useful immunogens for vaccination. The individual proteins found in these blebs can also be used as immunogens.

Claims (12)

1. A Shigella bacterium which expresses TolA, TolB, TolQ, and Pal proteins, does not express TolR protein, and does not express a native Shigella lipopolysaccharide , wherein the bacterium is Shigella sonnei or Shigella flexneri , and, during growth in culture medium, releases greater quantities of outer membrane blebs into the medium than the same bacterium expressing all of TolA, TolB, TolQ, TolR, and Pal proteins.

2. The Shigella bacterium of claim 1 , which is a ΔtolR strain of Shigella.

3. The Shigella bacterium of claim 2 , wherein the bacterium does not express a native Shigella lipopolysaccharide and does not express a native Shigella O antigen.

4. The Shigella bacterium of claim 1 , wherein the TolA, TolQ, and/or Pal protein is located in the bacterium's inner or outer membrane.

5. The Shigella bacterium of claim 1 , wherein the Shigella bacterium additionally does not express a Shigella enteric toxin.

6. The Shigella bacterium of claim 1 , which does not express the functional HtrB enzyme.

7. The Shigella bacterium of claim 6 , which is a htrB knockout.

8. The Shigella bacterium of claim 2 , wherein the bacterium is of a ΔtolRΔgalU strain.

9. The Shigella bacterium of claim 2 , wherein a stxA and/or stxB gene is inactivated.

10. Culture medium comprising a bacterium of claim 5 , which has been grown under conditions which permit the release of blebs into the medium by the bacterium.

11. A method of producing Shigella sonnei or Shigella flexneri blebs, comprising culturing the bacterium of claim 1 in a culture medium under conditions which permit the release of blebs into the medium by the bacterium and separating the released blebs from the culture medium.

12. The method of claim 11 , wherein the bacterium has been grown under iron-limiting conditions.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 5, 2017
From: GERKE, CHRISTIANE; SCORZA, FRANCESCO BERLANDA; SAUL, ALLAN; MAGGIORE, LUANA
To: NOVARTIS VACCINES INSTITUTE FOR GLOBAL HEALTH S.R.L.
Reel/Frame 043790/0737 →
CHANGE OF NAME Recorded Oct 5, 2017
From: NOVARTIS VACCINES INSTITUTE FOR GLOBAL HEALTH S.R.L.
To: GSK VACCINES INSTITUTE FOR GLOBAL HEALTH S.R.L.
Reel/Frame 043791/0001 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 5, 2017
From: GSK VACCINES INSTITUTE FOR GLOBAL HEALTH S.R.L.
To: NOVARTIS AG
Reel/Frame 044127/0918 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 5, 2017
From: NOVARTIS AG
To: GLAXOSMITHKLINE BIOLOGICALS SA
Reel/Frame 044135/0389 →
Priority Claims (1)
GB 0917002 · Sep 28, 2009 · national
Continuity (2)
Continuation 13498723
Related Publication 20160289632A1 · Oct 6, 2016