Vaccines for hsv-2

Abstract

Compositions of recombinant HSV-2 proteins and an agonist of the innate immune system, such as an adjuvant, are provided as a vaccine. Proteins include an envelope glycoprotein and a structural protein other than an envelope glycoprotein, e.g., a capsid or tegument protein. The vaccine is for use in either HSV-2 seropositive or seronegative subjects.

1 . An immunogenic fragment of an HSV-2 polypeptide selected from the group consisting of:
 (a) an immunogenic fragment of UL19 polypeptide lacking at least 75% of amino acids 1-450 of SEQ ID NO: 4 and lacking at least 75% of amino acids of 1055-1374 of SEQ ID NO: 4;   (b) the sequence set out in SEQ ID NO: 12;   (c) an immunogenic variant of (a) or (b) that retains at least 85% amino acid identity over at least 15 contiguous amino acids;   (d) an immunogenic fragment of (a) or (b); and   (e) a chimeric fusion of (a), (b) (c) or (d).   
     
     
         2 . An isolated polynucleotide encoding the polypeptide of  claim 1 . 
     
     
         3 . An immunogenic, pharmaceutical composition comprising:
 (i) an immunogenic fragment of an HSV-2 polypeptide selected from the group consisting of:
 (a) an immunogenic fragment of UL19 polypeptide lacking at least 75% of amino acids 1-450 of SEQ ID NO: 4 and lacking at least 75% of amino acids of 1055-1374 of SEQ ID NO: 4; 
 (b) the sequence set out in SEQ ID NO: 12; 
 (c) an immunogenic variant of (a) or (b) that retains at least 85% amino acid identity over at least 15 contiguous amino acids; 
 (d) an immunogenic fragment of (a) or (b); and 
 (e) a chimeric fusion of (a), (b) or (c); 
   (ii) optionally, an agent that activates innate immunity; and   (iii) a pharmaceutically acceptable carrier.   
     
     
         4 . The composition of  claim 3  which further comprises (i) UL25 or an immunogenic fragment thereof, (ii) gD2 or an immunogenic fragment thereof, or (iii) UL25 or an immunogenic fragment thereof and qD2 or an immunogenic fragment thereof. 
     
     
         5 . (canceled) 
     
     
         6 . The composition of any of  claim 4  wherein the agent is an adjuvant. 
     
     
         7 . The composition of  claim 6  wherein the adjuvant is GLA. 
     
     
         8 . The composition of  claim 7  wherein the GLA is in the form of an oil-in-water emulsion or is in an aqueous form. 
     
     
         9 . The composition of  claim 8  wherein the oil-in-water emulsion comprises squalene. 
     
     
         10 . A method for treating an HSV-2 infection in a subject comprising administering the composition of  claim 4  to the subject. 
     
     
         11 . A method of generating an immune response in a subject comprising administering the composition of  claim 4  to the subject. 
     
     
         12 . A method for immunizing a subject against HSV-2 comprising administering the composition of  claim 4  to the subject. 
     
     
         13 . The method of  claim 10  wherein the administration route is intradermal, mucosal, intramuscular, subcutaneous, sublingual, rectal, or vaginal. 
     
     
         14 . (canceled)