Vaccines against genital herpes simplex infections

1. A vaccine comprising a recombinant herpes simplex virus (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;

(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; and

(c) a gene encoding a foreign antigen;

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 foreign antigen is a protein antigen from a viral or bacterial pathogen of the host cell.

3. The vaccine of claim 1 , wherein the foreign antigen is capable of eliciting an immune response in a host cell against a mucosally transmitted pathogen.

4. The vaccine of claim 3 , wherein the mucosally transmitted pathogen is a pathogenic virus or a pathogenic bacterium.

5. The vaccine of claim 4 , wherein the pathogenic virus is not HSV.

6. The vaccine of claim 3 , wherein the mucosally transmitted pathogen is human immunodeficiency virus infection (HIV) or Chlamydia trachomatis.

7. The vaccine of claim 4 , wherein the vaccine is for treating and/or preventing diseases that are caused by the pathogenic virus or the pathogenic bacterium.

8. 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).

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

10. 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.

11. A method of immunizing a patient against a disease that is caused by a viral or bacterial pathogen, the method comprising the step of administering to the patient a therapeutically effective amount vaccine of claim 1 .

12. The method of claim 11 , wherein the patient is a human.

13. 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; and

(c) a gene encoding a foreign antigen;

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

14. The recombinant HSV genome of claim 13 , wherein the foreign antigen is a protein antigen from a viral or bacterial pathogen.

15. The recombinant HSV genome of claim 13 , wherein the foreign antigen is capable of eliciting an immune response in a host cell against a mucosally transmitted pathogen.

16. The recombinant HSV genome of claim 15 , wherein the mucosally transmitted pathogen is a pathogenic virus or a pathogenic bacterium.

17. The vaccine of claim 15 , wherein the mucosally transmitted pathogen is human immunodeficiency virus infection (HIV) or Chlamydia trachomatis.

18. An immunogenic composition or virus comprising the recombinant HSV genome of claim 13 .

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

(a) transfecting a host cell with a recombinant HSV genome comprising

(i) 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,

(ii) 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, and

(iii) a gene encoding a foreign antigen,

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

(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.

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

(a) transfecting a host cell with the recombinant HSV genome of claim 13 ; 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.