Live vaccine strains of Francisella

• US 8,323,664 B2
• Filed: 07/25/2007
• Issued: 12/04/2012
• Est. Priority Date: 07/25/2006
• Status: Expired due to Fees

• Current Assignee: Secretary of State For Defence
• Original Assignee: Secretary of State For Defence
• Inventors: Farquhar Oyston, Petra Claire, Titball, Richard William, Mitchell, Stephen Lloyd
• Primary Examiner(s): BASKAR, PADMAVATHI
• Application Number:
  US12/374,888
• Publication Number:
  US 20100021501A1
• Time in Patent Office: 1,959 Days
• Field of Search: None
• US Class Current: 424/234.1
• 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 comprise 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. A method of stimulating an immune response against or treating infection caused by Francisella tularensis, comprising administering to an animal an effective amount of a strain of Francisella tularensis wherein capB or capC gene has been inactivated by deletion, and wherein administration of the effective amount of the strain is able to produce an immune response in an animal.

3. The method of claim 1 wherein the strain of Francisella tularensis is a subspecies selected from the group consisting of tularensis, holarctica and tularensis SchuS4.

4. The method of claim 1 wherein the strain comprises a further deletion of a gene that encodes another component of the cell.

5. The method of claim 4 wherein the gene which encodes for another component of the cell is selected from the group consisting of FTT0918, FTT0919 and FTT1564.

6. The method of claim 4 wherein the gene that encodes for another component of the cell is a gene that encodes for a pilin subunit or is a gene that encodes for an enzyme in the purine pathway.

7. The method of claim 4 wherein the gene that encodes for another component of the cell is a gene selected from the group consisting of pilA, pilE, pilC, purA and purF.

2. A method of stimulating an immune response against or treating infection caused by Francisella tularensis, comprising administering to an animal an effective amount of a pharmaceutical composition comprising a live strain of a Francisella tularensis wherein capB or capC gene has been inactivated by deletion, and wherein administration of the effective amount of the strain is able to produce an immune response in an animal, in combination with a pharmaceutically acceptable carrier.

8. The method of claim 2 wherein the strain of Francisella tularensis is a subspecies selected from the group consisting of tularensis, holarctica and tularensis SchuS4.