Vaccines against genital herpes simplex infections

Abstract

The present invention provides vaccines for treating or preventing a herpes simplex virus infection and methods of using and making the vaccine. Further provided are recombinant herpes simplex virus genomes, recombinant viruses, and immunogenic compositions.

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 at least one modification in each of the UL53 and UL20 genes and 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 at least one modification is selected from the group consisting of an insertion, a substitution, and a deletion. 
     
     
         5 . The vaccine of  claim 1 , wherein the modified UL53 gene comprises a deletion. 
     
     
         6 . The vaccine of  claim 1 , wherein the modified UL20 gene comprises a deletion. 
     
     
         7 . The vaccine of  claim 1 , wherein the deletion in the modified UL53 corresponds to the portion of the UL53 gene encoding the amino terminal region of glycoprotein K (gK). 
     
     
         8 - 10 . (canceled) 
     
     
         11 . The vaccine of  claim 1 , wherein the recombinant HSV 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).   
     
     
         12 . The vaccine of  claim 1 , wherein the recombinant HSV is a live virus. 
     
     
         13 . The vaccine of  claim 1 , wherein the HSV infection comprises a genital HSV infection. 
     
     
         14 . The vaccine of  claim 1 , wherein the HSV infection comprises or further comprises an orofacial HSV infection. 
     
     
         15 . The vaccine of  claim 1 , 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. 
     
     
         16 . 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 . 
     
     
         17 . (canceled) 
     
     
         18 . A recombinant herpes simplex virus (HSV) genome comprising at least one modification in each of the UL53 and UL20 genes and wherein a virus comprising the genome is capable of replication in a host cell and incapable of entry into axonal compartments of neurons. 
     
     
         19 - 27 . (canceled) 
     
     
         28 . The recombinant HSV genome of  claim 18 , 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).   
     
     
         29 . The recombinant HSV genome of  claim 18 , comprising an additional gene encoding an antigen. 
     
     
         30 - 32 . (canceled) 
     
     
         33 . An immunogenic composition comprising the recombinant HSV genome of  claim 18 . 
     
     
         34 - 36 . (canceled) 
     
     
         37 . A virus comprising the recombinant HSV genome of  claim 18 . 
     
     
         38 . (canceled) 
     
     
         39 . A method for producing a vaccine or immunogenic composition, the method comprising:
 (a) transfecting a host cell with a recombinant HSV genome, wherein the recombinant HSV genome comprises at least one modification in each of the UL53 and UL20 genes and 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.   
     
     
         40 . (canceled) 
     
     
         41 . A method for producing a recombinant HSV, the method comprising:
 (a) transfecting a host cell with the recombinant HSV genome of  claim 18 ; 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.   
     
     
         42 - 43 . (canceled)