Vaccines for HSV-2
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. A method for treating an Herpes Simplex virus type 2 infection (HSV-2) in a subject, comprising administering to the subject an immunogenic pharmaceutical composition comprising,
(i) (a) an immunogenic fragment of an Herpes Simplex virus type 2 (HSV-2) UL19 polypeptide wherein the immunogenic fragment of UL19 comprises the amino acid sequence set forth in SEQ ID NO:12,
wherein the immunogenic fragment of (i)(a) lacks at least 75% of amino acids 1-450 of SEQ ID NO: 4 and lacks at least 75% of amino acids of 1055-1374 of SEQ ID NO: 4 or an immunogenic variant thereof that retains at least 90% amino acid identity over the full length of the immunogenic fragment,
(b) glycoprotein D of HSV-2 (gD2), wherein the gD2 comprises the amino acid sequence set forth in SEQ ID NO:2 or 3, or an immunogenic fragment thereof comprising at least 15 contiguous amino acids of SEQ ID NO: 2 or 3,
(c) and UL25, wherein the UL25 comprises the amino acid sequence set forth in SEQ ID NO:5 or an immunogenic fragment thereof comprising at least 15 contiguous amino acids of SEQ ID NO: 5; and
(ii) Glucopyranosyl Lipid Adjuvant (GLA).
2. A method for generating an immune response to HSV-2 in a subject, comprising administering to the subject an immunogenic pharmaceutical composition comprising,
(i) (a) an immunogenic fragment of an Herpes Simplex virus type 2 (HSV-2) UL19 polypeptide wherein the immunogenic fragment of UL19 comprises the amino acid sequence set forth in SEQ ID NO:12 ,
wherein the immunogenic fragment of (i)(a) lacks at least 75% of amino acids 1-450 of SEQ ID NO: 4 and lacks at least 75% of amino acids of 1055-1374 of SEQ ID NO: 4 or an immunogenic variant thereof that retains at least 90% amino acid identity over the full length of the immunogenic fragment,
(b)glycoprotein D of HSV-2 (gD2), wherein the gD2 comprises the amino acid sequence set forth in SEQ ID NO:2 or 3, or an immunogenic fragment thereof comprising at least 15 contiguous amino acids of SEQ ID NO: 2 or 3,
(c) and UL25, wherein the UL25 comprises the amino acid sequence set forth in SEQ ID NO:5 or an immunogenic fragment thereof comprising at least 15 contiguous amino acids of SEQ ID NO: 5; and
(ii) Glucopyranosyl Lipid Adjuvant (GLA).
3. The method of claim 1 , wherein the immunogenic fragment of an HSV-2 UL19 polypeptide has the amino acid sequence set forth in SEQ ID NO:12.
4. The method of claim 1 , wherein the immunogenic pharmaceutical composition further comprises one or more HSV-2 proteins, or an immunogenic fragment thereof, selected from the group consisting of UL47, ICPO, UL46, UL39, UL7 and UL26.
5. The method of claim 1 , wherein the GLA is in the form of an oil-in-water emulsion or is in an aqueous form.
6. The method of claim 1 , wherein the immunogenic pharmaceutical composition further comprises a second adjuvant.
7. The method of claim 6 , wherein the second adjuvant is selected from the group consisting of a TLR7 agonist, a TLR9 agonist, alum; an emulsion; a saponin; a cytokine; an unmethylated CpG dinucleotide; and a modified saponin.
8. The method of claim 6 , wherein the second adjuvant is an oil-in-water emulsion.
9. The method of claim 2 , wherein the immunogenic fragment of an HSV-2 UL19 polypeptide has the amino acid sequence set forth in SEQ ID NO:12.
10. The method of claim 2 , wherein the immunogenic pharmaceutical composition further comprises one or more HSV-2 proteins, or an immunogenic fragment thereof, selected from the group consisting of UL47, ICP0, UL46, UL39, UL7 and UL26.
11. The method of claim 2 , wherein the GLA is in the form of an oil-in-water emulsion or is in an aqueous form.
12. The method of claim 2 , wherein the immunogenic pharmaceutical composition further comprises a second adjuvant.
13. The method of claim 12 , wherein the second adjuvant is selected from the group consisting of a TLR7 agonist, a TLR9 agonist, alum; an emulsion; a saponin; a cytokine; an unmethylated CpG dinucleotide; and a modified saponin.
14. The method of claim 12 , wherein the second adjuvant is an oil-in-water emulsion.