Vaccines against genital herpes simplex infections

1. A vaccine for treating or preventing a herpes simplex virus (HSV) infection, the vaccine comprising a recombinant HSV, wherein the recombinant HSV comprises a recombinant HSV genome comprising:

(a) a modified UL53 gene comprising a deletion corresponding to the region of the UL53 gene that encodes amino acids 31-68 of wild-type gK; and

(b) a modified UL20 gene comprising a deletion corresponding to the region of the UL20 gene that encodes amino acids 4-22 of wild-type UL20 protein;

wherein the recombinant HSV is capable of replication in a host cell and incapable of entry into axonal compartments of neurons.

2. The vaccine of claim 1 , wherein the recombinant HSV genome is derived from the genome of HSV-1 or HSV-2.

3. The vaccine of claim 2 , wherein HSV-1 is HSV-1 strain F.

4. The vaccine of claim 1 , wherein the genome comprises a member selected from the group consisting of:

(a) the nucleotide sequence set forth in SEQ ID NO: 5;

(b) a nucleotide sequence comprising at least 90% identity to the nucleotide sequence set forth in SEQ ID NO: 5;

(c) a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 6;

(d) a nucleotide sequence encoding an amino acid sequence comprising at least 90% identity to the amino acid sequence set forth in SEQ ID NO: 6;

(e) the nucleotide sequence set forth in SEQ ID NO: 7;

(f) a nucleotide sequence comprising at least 90% identity to the nucleotide sequence set forth in SEQ ID NO: 7;

(g) a nucleotide sequence encoding the amino acid sequence set forth in SEQ ID NO: 8;

(h) a nucleotide sequence encoding an amino acid sequence comprising at least 90% identity to the amino acid sequence set forth in SEQ ID NO: 8; and

(i) the nucleotide sequence of (a), (b), (c), or (d) and the nucleotide sequence of (e), (f), (g), or (h).

5. The vaccine of claim 1 , wherein the recombinant HSV is a live virus.

6. The vaccine of claim 1 , wherein the HSV infection comprises a genital HSV infection.

7. The vaccine of claim 1 , wherein the HSV infection comprises or further comprises an orofacial HSV infection.

8. The vaccine of claim 1 , further comprising a pharmaceutically acceptable component selected from the group consisting of a carrier, an excipient, a stabilizing agent, a preservative, an immunostimulant, and an adjuvant.

9. A method of immunizing a patient against an HSV infection comprising the step of administering to the patient a therapeutically effective amount of the vaccine of claim 1 .

10. An recombinant herpes simplex virus (HSV) genome comprising:

(a) a modified UL53 gene comprising a deletion corresponding to the region of the UL53 gene that encodes amino acids 31-68 of wild-type gK; and

(b) a modified UL20 gene comprising a deletion corresponding to the region of the UL20 gene that encodes amino acids 4-22 of wild-type UL20 protein;

wherein a virus comprising the genome is capable of replication in a host cell and incapable of entry into axonal compartments of neurons.

11. An immunogenic composition or virus comprising the recombinant HSV genome of claim 10 .

12. A method for producing a vaccine or immunogenic composition, the method comprising:

(a) transfecting a host cell with the recombinant HSV genome of claim 10 ;

(b) incubating the transfected host cell under conditions favorable for the formation of a recombinant HSV virus comprising the recombinant HSV genome;

(c) purifying the recombinant HSV virus comprising the recombinant HSV genome; and optionally

(d) combining the purified recombinant HSV virus with at least one pharmaceutically acceptable component.

13. A method for producing a recombinant HSV, the method comprising:

(a) transfecting a host cell with the recombinant HSV genome of claim 10 ; and

(b) incubating the transfected host cell under conditions favorable for the formation of a recombinant HSV virus comprising the recombinant HSV genome, whereby a recombinant HSV is produced.