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 an HSV-2 infection in a mammal comprising administering to the mammal:
(a) a priming preparation comprising a vector encoding an HSV-2 antigen under the control of a promoter;
(b) a first boosting preparation comprising the HSV-2 antigen encapsulated in liposomes; and
(c) a second boosting preparation comprising the vector encoding the HSV-2 antigen and the HSV-2 antigen encapsulated in liposomes,
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 herpatic 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 herpatic lesions is reduced and/or completely prevented 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 gD protein 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 HSV-2 antigen is a gD glycoprotein.
20 . The method of claim 1 , wherein the vector encodes a full-length gD glycoprotein sequence.
21 . The method of claim 20 , wherein the full-length gD glycoprotein sequence comprises a sequence of SEQ ID NO: 1.
22 . The method of claim 1 , wherein the liposomal-encapsulated antigen in the first and second boosting preparations is an extracellular domain of a gD glycoprotein.
23 . The method of claim 22 , wherein the antigen comprises a sequence of SEQ ID NO: 2.
24 . The method of claim 1 , wherein the liposomes are anionic liposomes.
25 . The method of claim 24 , wherein the liposomes have an average diameter of about 0.5-5 μm.
26 . The method of claim 1 , wherein the mammal is human.