Mutants of replication competent vaccinia virus
First Claim
1. A recombinant vaccinia virus comprising:
- a first recombinant nucleic acid comprising a first expression control sequence and a nucleic acid encoding a conditional replication gene product wherein the first expression control sequence is operably linked to the nucleic acid encoding the conditional replication gene product; and
a second recombinant nucleic acid comprising a second expression control sequence and a nucleic acid encoding a transcription factor that conditionally binds the first expression control sequence wherein the second expression control sequence is operably linked to the nucleic acid encoding a transcription factor, and wherein the second recombinant nucleic acid is in a non-essential region of the vaccinia virus genome.
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Accused Products
Abstract
The present invention relates to vaccines having an increased level of safety comprising recombinant vaccinia viruses. The invention also relates to methods for stimulating a protective immune response in an immunized host using the vaccines of the invention. The vaccines and recombinant vaccinia viruses of the invention comprise a first nucleic acid comprising an expression control sequence and a second nucleic acid comprising an exogenous nucleic acid encoding a conditional replication gene product, wherein the expression control sequence is operably linked to the exogenous nucleic acid. The exogenous nucleic acid may, by its expression or non-expression, confer upon the recombinant vaccinia virus either sensitivity or dependence upon an exogenous molecule (e.g. a drug) or a condition. Importantly, to allow the recombinant vaccinia viruses of the invention to replicate normally under permissive conditions, the exogenous nucleic acid is inserted into a non-essential locus, e.g., the E2L/E3L inter-genic locus, K1L/K2L inter-genic locus, the superoxide dismutate locus, and the 7.5 K locus.
13 Citations
41 Claims
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1. A recombinant vaccinia virus comprising:
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a first recombinant nucleic acid comprising a first expression control sequence and a nucleic acid encoding a conditional replication gene product wherein the first expression control sequence is operably linked to the nucleic acid encoding the conditional replication gene product; and
a second recombinant nucleic acid comprising a second expression control sequence and a nucleic acid encoding a transcription factor that conditionally binds the first expression control sequence wherein the second expression control sequence is operably linked to the nucleic acid encoding a transcription factor, and wherein the second recombinant nucleic acid is in a non-essential region of the vaccinia virus genome. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 24, 25)
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17. A recombinant vaccinia virus comprising:
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a nucleic acid comprising an expression control sequence and an exogenous nucleic acid encoding a conditional replication gene product, wherein the expression control sequence is operably linked to the exogenous nucleic acid and wherein the nucleic acid is in a non-essential region of the vaccinia virus genome. - View Dependent Claims (18, 19, 20, 21, 22, 23)
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26. A recombinant vaccinia virus comprising:
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a first nucleic acid comprising a vaccinia virus early/late promoter and a tetR gene, wherein the vaccinia virus early/late promoter is operably linked to the tetR gene; and
a second nucleic acid comprising a recombinant A14 gene and a tet response element, wherein the tet response element is operably positioned between the A14 transcriptional start site and the A14 translational start site, wherein the first nucleic acid is in a non-essential region of the vaccinia virus genome. - View Dependent Claims (27, 28)
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29. A recombinant vaccinia virus comprising:
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a first nucleic acid comprising a vaccinia virus early/late promoter and a reverse tetR gene, wherein the vaccinia virus early/late promoter is operably linked to the reverse tetR gene; and
a second nucleic acid comprising a recombinant A14 gene and a tet response element, wherein the tet response element is operably positioned between the A14 transcriptional start site and the A14 translational start site, wherein the first nucleic acid is in a non-essential region of the vaccinia virus genome. - View Dependent Claims (30, 31, 32)
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33. A recombinant vaccinia virus comprising:
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a first nucleic acid comprising a vaccinia virus late promoter and a tetR gene, wherein the vaccinia virus late promoter is operably linked to the tetR gene; and
a second nucleic acid comprising an expression control sequence comprising a tet response element and the PKR gene, wherein the tet response element is operably linked to the PKR gene, wherein the first and second nucleic acids are in non-essential regions of the vaccinia virus genome. - View Dependent Claims (34, 35, 36)
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37. A recombinant vaccinia virus comprising:
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a first nucleic acid comprising a vaccinia virus early/late promoter and a reverse tetR gene, wherein the vaccinia virus early/late promoter is operably linked to the reverse tetR gene; and
a second nucleic acid comprising an expression control sequence comprising a tet response element and the PI<
R gene, wherein the tet response element is operably linked to the PKR gene,wherein the first and second nucleic acids are in non-essential regions of the vaccinia virus genome. - View Dependent Claims (38, 39)
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40. A recombinant vaccinia virus comprising:
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a nucleic acid comprising a vaccinia virus early/late promoter and a UL97 gene, wherein the vaccinia virus early/late promoter is operably linked to the UL97 gene, wherein the nucleic acid is in a non-essential region of the vaccinia virus genome.
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41. A recombinant vaccinia virus comprising:
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a nucleic acid comprising a vaccinia virus early/late promoter and an acyclovir-sensitivity gene, wherein the vaccinia virus early/late promoter is operably linked to the acyclovir-sensitivity gene, wherein the nucleic acid is in a non-essential region of the vaccinia virus genome.
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Specification