Vaccines against genital herpes simplex infections

1. 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 glycoprotein K (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;

(c) a deletion of a non-essential HSV gene; and

(d) a gene encoding a heterologous antigen;

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

2. An immunogenic composition or virus comprising 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;

(c) a deletion of a non-essential HSV gene; and

(d) a gene encoding a heterologous antigen;

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

3. 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;

iii. a deletion of a non-essential HSV gene, and

iv. a gene encoding a heterologous antigen,

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

(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.

4. A method for producing a recombinant HSV, 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,

iii. a deletion of a non-essential HSV gene, and

iv. a gene encoding a heterologous antigen,

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

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

6. The recombinant HSV genome of claim 5 , wherein HSV-1 is HSV-1 strain F.

7. The recombinant HSV genome 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).

8. The recombinant HSV genome of claim 1 , wherein the heterologous antigen is capable of eliciting an immune response is a host cell against a pathogenic virus or a pathogenic bacterium.

9. The recombinant HSV genome of claim 8 , wherein the host cell is a human cell.