Live vaccine strain

• US 8,790,910 B2
• Filed: 11/09/2012
• Issued: 07/29/2014
• Est. Priority Date: 07/25/2006
• Status: Active Grant

• Current Assignee: Secretary of State For Defence
• Original Assignee: Secretary of State For Defence
• Inventors: Michell, Stephen Lloyd, Oyston, Petra Claire Farquhar, Titball, Richard William
• Primary Examiner(s): Baskar, Padma V
• Application Number:
  US13/673,233
• Publication Number:
  US 20130122573A1
• Time in Patent Office: 627 Days
• Field of Search: 424/234.1, 435/252.1, 536/23.1
• US Class Current: 435/252.3
• CPC Class Codes: A61K 2039/522 avirulent or attenuated
• CPC Class Codes: A61K 39/0208 Specific bacteria not otherwise provided for
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: C12N 1/36 Adaptation or attenuation of cells
• CPC Class Codes: C12N 15/52 Genes encoding for enzymes or proenzymes
• CPC Class Codes: C12N 15/74 Vectors or expression systems specially adapted for prokaryotic hosts other than E. coli, e.g. Lactobacillus, Micromonospora
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

A strain of Francisella species wherein a gene which encodes for part of the glutamate metabolic pathway has been inactivated, and which is able to produce a protective immune response in an animal, for use as live prophylactic or therapeutic vaccine against infection by said Francisella species. Particularly effective strains include those where the capB gene is deleted. Other embodiments of the invention describe strains which compromise a further genetic mutation wherein a gene which encodes for another component of the cell is also inactivated. Pharmaceutical compositions comprising said strains, together with methods which utilize such strains are also described and claimed.

Claims

1. An isolated strain of Francisella tularensis, subspecies tularensis or holarctica, wherein gene capB was inactivated by deletion.

2. The isolated strain of claim 1, wherein the isolated strain is a strain of Francisella tularensis subspecies tularensis.

3. The isolated strain of claim 1, wherein the isolated strain is a strain of Francisella tularensis subspecies holarctica.

4. The isolated strain of claim 1, wherein the isolated strain is a strain of Francisella tularensis subspecies tularensis SchuS4.

5. The strain of claim 1, wherein the isolated strain comprises an inactivated gene other than capB.

6. The isolated strain of claim 5, wherein the gene other than capB or is selected from the group consisting of FTT0918, FTT0919 and FTT1564.

7. The isolated strain of claim 5, wherein the gene other than capB or is a gene which encodes for a pilin subunit or is a gene which encodes for an enzyme in the purine pathway.

8. The isolated strain of claim 5, wherein the gene other than capB or is a gene selected from the group consisting of pilA, pilE, pilC, purA and purF.

9. The isolated strain of claim 1, wherein the isolated strain is able to stimulate an immune response to Francisella tularensis infection in an animal when administered to the animal.

10. A pharmaceutical composition comprising the isolated strain of claim 1.

11. A pharmaceutical composition comprising the isolated strain of claim 5.