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US 2025/0367279 A1Published application
Recombinant herpes simplex virus-2 expressing glycoprotein d and b antigens
AssigneeThe Brigham and Women's Hospital, Inc.
InventorFeng Yao
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Abstract
Provided herein are recombinant Herpes Simplex Virus-2 comprising sequences encoding glycoprotein D and B antigens, with two sequences encoding dominant negative UL9 proteins, compositions comprising the same, and methods of use thereof.
Claims16
A replication-defective Herpes simplex virus 2 (HSV-2) recombinant virus, comprising within its genome:
- a) a sequence comprising a codon optimized HSV-2 glycoprotein B2 (gB2) coding sequence operably linked to an ICP0 promoter that is operably linked to a tetO sequence, wherein the gB2 coding sequence is inserted at the gG2 locus of the HSV-2 genome;
- b) a sequence comprising a codon-optimized HSV-2 glycoprotein D2 (gD2) coding sequence operably linked to an HSV-1 or HSV-2 immediate early promoter, wherein the gD2 coding sequence is inserted at the ICP0 locus;
- c) a sequence comprising a first coding sequence encoding a dominant negative mutant HSV-1 or HSV-2 UL9 protein (dnUL9) operably linked to a ICP27 promoter that is operably linked to a tetO sequence and a codon-optimized gD2 sequence operably linked to an ICP4 promoter that is operably linked to a tetO sequence, wherein the dnUL9/gD2 sequence is inserted into the intergenic region of the HSV-2 UL26 and UL27 genes;
- and
- d) a sequence comprising a second dnUL9 coding sequence operably linked to an ICP4 promoter that is operably linked to a tetO sequence wherein the second UL9-C535C coding sequence is inserted at the gD2 locus,
- wherein the genome of the virus does not comprise a sequence encoding a functional endogenous ICP0 protein, a functional endogenous HSV-2 gG2 protein.
3 more elements
-20. (canceled)
Dependencies are inferred from the claim text.