HSV-1 and HSV-2 vaccines and methods of use thereof
This invention provides methods of vaccinating a subject against a Herpes Simplex Virus (HSV) infection and disorders and symptoms associated with same, and impeding, inhibiting, reducing the incidence of, and suppressing HSV infection, neuronal viral spread, formation of zosteriform lesions, herpetic ocular disease, herpes-mediated encephalitis, and genital ulcer disease in a subject, comprising the step of contacting the subject with a mutant strain of the HSV, containing an inactivating mutation in a gene encoding a gE, gI, Us9, or other proteins.
1. An immunogenic composition comprising a mutant Herpes Simplex Virus type 2 (HSV-2) consisting of a single inactivating mutation in the Us8 gene, wherein said inactivating mutation is a deletion of base pairs (bp) 369-1479 of SEQ ID NO: 7, wherein said immunogenic composition induces an anti-HSV immune response in a subject.
2. A method of treating, reducing the pathogenesis of, or ameliorating the primary or secondary symptoms of a Herpes Simplex Virus (HSV) infection in a subject, comprising the step of inoculating said subject with a composition comprising the mutant HSV-2 of claim 1 .
3. The method of claim 2 , wherein said HSV infection is an HSV-1 infection or an HSV-2 infection.
4. The method of claim 2 , wherein the neuronal viral spread of said mutant strain is impeded.
5. The method of claim 2 , wherein said mutant strain is replication-competent in the skin tissue of said subject.
6. The method of claim 2 , wherein said HSV infection is a genital HSV infection, HSV encephalitis, an HSV ocular infection, HSV labialis, or a combination thereof.
7. The method of claim 2 , wherein said subject is infected by or is at risk for infection by HSV.
8. The method of claim 2 , wherein said treating, reducing the pathogenesis of, or ameliorating the primary or secondary symptoms of a Herpes Simplex Virus (HSV) infection is by inducing an anti-HSV immune response in said subject.
9. The method of claim 8 , wherein said anti-HSV immune response is an anti-HSV neutralizing antibody response.
10. The method of claim 2 , wherein the step of contacting comprises epidermal, intramuscular, subcutaneous, or intra-respiratory mucosal injection.
11. The mutant HSV-2 of claim 1 , wherein said HSV-2 is strain 2.12.
12. The mutant HSV-2 of claim 1 , wherein said mutant HSV has a defect in neuronal spread in the anterograde and retrograde directions.