Therapeutic vaccines for treating herpes simplex virus type-2 infections

Abstract

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.