Vaccines and Immunomodulatory Therapies for Tularemia
AssigneeUniversity of Maryland, Baltimore
InventorsAraceli Santiago, Myron M. Levine, Eileen M. Barry
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Abstract
The present invention relates to attenuated strains of Francisella tularensis from which genes in the guanine nucleotide biosynthetic pathway have been deleted and to methods for making the mutants. The invention further relates to the use of the attenuated strains to make vaccines.
Claims24
A strain of Francisella tularensis that cannot form de novo guanine nucleotides, wherein said strain has a non-functional guaA gene.
A strain of F. tularensis that cannot form de novo guanine nucleotides, wherein said strain has a non-functional guaB gene.
A strain of F. tularensis that cannot form de novo guanine nucleotides, wherein said strain has a non-functional guaA gene and has a non-functional guaB gene.
A vaccine formulation comprising:
- (a) a pharmaceutically effective amount of a strain of F. tularensis that cannot form de novo guanine nucleotides, wherein said strain has a non-functional guaA gene, or a non-functional guaB gene, or both a non-functional guaA gene and has a non-functional guaB gene, and
- (b) a pharmaceutically acceptable carrier or diluent.
A pFT724 guaB suicide plasmid.
A pFT695 guaA suicide plasmid.
A pFT758 guaA suicide plasmid.
A method for treating tularemia in an animal, comprising blocking expression of the guaA gene of F. tularensis by administering to an animal in need of treatment a therapeutically effective amount of an antisense oligonucleotide that is sufficiently complementary to the guaA gene of F. tularensis to permit specific hybridization under physiologic conditions and wherein said antisense nucleic acid inhibits expression of the guaA gene, thereby treating tularemia in an animal.
A method for treating tularemia in an animal, comprising blocking expression of the guaB gene of F. tularensis by administering to an animal in need of treatment a therapeutically effective amount of an antisense oligonucleotide that is sufficiently complementary to the guaB gene of F. tularensis to permit specific hybridization under physiologic conditions and wherein said antisense nucleic acid inhibits expression of the guaB gene, thereby treating tularemia in an animal.
A method for treating tularemia in an animal, comprising blocking translation of messenger RNA produced from the guaA gene of F. tularensis by administering to an animal in need of treatment a therapeutically effective amount of an antisense oligonucleotide that is sufficiently complementary to messenger RNA produced from the guaA gene to permit specific hybridization under physiologic conditions to the messenger RNA, and wherein said antisense nucleic acid inhibits translation of the messenger RNA, thereby treating tularemia in an animal.
A method for preventing tularemia in an animal, comprising blocking translation of messenger RNA produced from the guaA gene of F. tularensis by administering to an animal in need of prevention a therapeutically effective amount of an antisense oligonucleotide that is sufficiently complementary to messenger RNA produced from the guaA gene to permit specific hybridization under physiologic conditions to the messenger RNA, and wherein said antisense nucleic acid inhibits translation of the messenger RNA, thereby preventing tularemia in an animal.
A method for treating tularemia in an animal, comprising blocking translation of messenger RNA produced from the guaB gene of F. tularensis by administering to an animal in need of treatment a therapeutically effective amount of an antisense oligonucleotide that is sufficiently complementary to messenger RNA produced from the guaB gene to permit specific hybridization under physiologic conditions to the messenger RNA, and wherein said antisense nucleic acid inhibits translation of the messenger RNA, thereby treating tularemia in an animal.
A method for preventing tularemia in an animal, comprising blocking translation of messenger RNA produced from the guaB gene of F. tularensis by administering to an animal in need of prevention a therapeutically effective amount of an antisense oligonucleotide that is sufficiently complementary to messenger RNA produced from the guaB gene to permit specific hybridization under physiologic conditions to the messenger RNA, and wherein said antisense nucleic acid inhibits translation of the messenger RNA, thereby preventing tularemia in an animal.
An isolated polynucleotide molecule comprising a polynucleotide molecule selected from the group consisting of:
- (i) the F. tularensis guaA gene polynucleotide sequence set forth in SEQ ID NO:1,
- (ii) an isolated polynucleotide molecule comprising a polynucleotide sequence having at least 95% identity to the polynucleotide set forth in SEQ ID NO:1, and
- (iii) an isolated polynucleotide molecule comprising a polynucleotide sequence that hybridizes under stringent hybridization conditions to a complement of the polynucleotide set forth in SEQ ID NO:1.
An isolated polynucleotide molecule comprising a polynucleotide molecule selected from the group consisting of:
- (i) the F. tularensis guaB gene polynucleotide sequence set forth in SEQ ID NO:2,
- (ii) an isolated polynucleotide molecule comprising a polynucleotide sequence having at least 95% identity to the polynucleotide set forth in SEQ ID NO:2, and
- (iii) an isolated polynucleotide molecule comprising a polynucleotide sequence that hybridizes under stringent hybridization conditions to a complement of the polynucleotide set forth in SEQ ID NO:2.
Dependencies are inferred from the claim text.