Therapeutic vaccines for treating herpes simplex virus type-2 infections
The invention provides methods and kits for inducing a therapeutic immunity in animals (e.g. mammals) against viral antigens, including herpes-simplex virus type 2. In particular, the invention provides a method of treating animals with an established HSV-2 infection by administering a therapeutic vaccine comprising a priming dose of a nucleic acid encoding an HSV-2 antigen, an initial or first boosting dose comprising the protein form of the antigen encapsulated in liposomes, and one or more subsequent boosting doses comprising both the nucleic acid encoding the HSV-2 antigen and the liposomal-encapsulated protein antigen.
1. A method for treating a herpes simplex virus type 2 (HSV-2) infection in a mammal, wherein the method comprises the steps of:
(a) administering to the mammal a priming preparation comprising a vector encoding an HSV-2 antigen under the control of a promoter, wherein the vector encodes a full-length gD sequence comprising a sequence of SEQ ID NO: 1;
(b) after step (a), administering to the mammal a first boosting preparation comprising the HSV-2 antigen encapsulated in liposomes; and
(c) after step (b), administering to the mammal a second boosting preparation comprising the vector encoding the HSV-2 antigen and the liposomal-encapsulated HSV-2 antigen,
wherein the vector is administered intramuscularly and the liposomal-encapsulated antigen is administered intranasally.
2. The method of claim 1 , wherein the priming preparation is administered in one or two administrations.
3. The method of claim 1 , wherein the first boosting preparation is administered to the mammal about 2 to 4 weeks after the priming preparation.
4. The method of claim 1 , wherein the first boosting preparation is administered to the mammal about 7 to 18 days after the priming preparation.
5. The method of claim 4 , wherein the first boosting preparation is administered to the mammal about 10 to 16 days after the priming preparation.
6. The method of claim 1 , wherein the second boosting preparation is administered to the mammal about 2 to 4 weeks after the first boosting preparation.
7. The method of claim 1 , wherein the second boosting preparation is administered to the mammal about 7 to 18 days after the first boosting preparation.
8. The method of claim 7 , wherein the second boosting preparation is administered to the mammal about 10 to 16 days after the first boosting preparation.
9. The method of claim 1 , further comprising administering to the mammal a combination of the vector encoding the HSV-2 antigen and the HSV-2 antigen encapsulated in liposomes at the sign of recurrence of herpetic lesions.
10. The method of claim 1 , wherein one or more symptoms of HSV-2 infection is ameliorated in the mammal following administration of the second boosting preparation.
11. The method of claim 10 , wherein the recurrence of herpetic lesions is reduced in the mammal as compared to an untreated mammal or a mammal vaccinated with a non-mucosal vaccine.
12. The method of claim 10 , wherein viral shedding is reduced in the mammal as compared to an untreated mammal or a mammal vaccinated with a non-mucosal vaccine.
13. The method of claim 1 , wherein antigen-specific IgA and IgG is increased in the vaginal secretions of the mammal as compared to an untreated mammal or a mammal vaccinated with a non-mucosal vaccine.
14. The method of any one of claims 11 to 13 , wherein the non-mucosal vaccine comprises a truncated HSV-2 glycoprotein D (gD) formulated for subcutaneous administration.
15. The method of claim 1 , wherein the promoter is a cytomegalovirus promoter.
16. The method of claim 15 , wherein the cytomegalovirus promoter is an immediate early promoter.
17. The method of claim 1 , wherein the HSV-2 antigen encoded by the vector is codon-optimized for expression in mammalian cells.
18. The method of claim 1 , wherein the HSV-2 antigen encoded by the vector is codon-optimized for expression in human cells.
19. The method of claim 1 , wherein the liposomal-encapsulated antigen in the first and second boosting preparations is an extracellular domain of gD.
20. The method of claim 19 , wherein the antigen comprises a sequence of SEQ ID NO: 2.
21. The method of claim 1 , wherein the liposomes are anionic liposomes.
22. The method of claim 21 , wherein the liposomes have an average diameter of about 0.5-5 μm.
23. The method of claim 1 , wherein the mammal is human.
24. A method for treating a herpes simplex virus type 2 (HSV-2) infection in a mammal, wherein the method comprises the steps of:
(a) administering to the mammal a priming preparation comprising a vector encoding an HSV-2 antigen under the control of a promoter, wherein the vector encodes a full-length gD sequence comprising a sequence of SEQ ID NO: 1;
(b) after step (a), administering to the mammal a first boosting preparation comprising the HSV-2 antigen encapsulated in liposomes, wherein the liposomal-encapsulated antigen is an extracellular domain of gD comprising a sequence of SEQ ID NO: 2; and
(c) after step (b), administering to the mammal a second boosting preparation comprising the vector encoding the HSV-2 antigen and the liposomal-encapsulated HSV-2 antigen,
wherein the vector is administered intramuscularly and the liposomal-encapsulated antigen is administered intranasally.