Vaccine comprising beta-herpesvirus

Abstract

The present invention relates to a beta-herpesvirus, preferably a recombinant beta-herpesvirus, wherein the beta-herpesvirus comprises at least one heterologous nucleic acid, wherein the at least one heterologous nucleic acid comprises a gene encoding a cellular ligand.

What is claimed is: 
     
         1 . A beta-herpesvirus, preferably a recombinant beta-herpesvirus, wherein the beta-herpesvirus comprises at least one heterologous nucleic acid, wherein the at least one heterologous nucleic acid comprises a gene encoding a cellular ligand. 
     
     
         2 . The beta-herpesvirus according to  claim 1 , wherein the cellular ligand is capable of binding a receptor for the cellular ligand wherein the receptor for the cellular ligand is present on the surface of at least one immune cell, and wherein the at least one immune cell is selected from the group consisting of NK cells, γδ T cells and activated CD8 +  T cells. 
     
     
         3 . The beta-herpesvirus according to  claim 1 , wherein the cellular ligand is an NKG2D ligand. 
     
     
         4 . The beta-herpesvirus according to  claim 3 , wherein the NKG2D ligand is a human NKG2D ligand is selected from the group consisting of UL16 binding proteins and MHC class-1-related protein. 
     
     
         5 . The beta-herpesvirus according to  claim 4 , wherein the UL16 binding protein is selected from the group consisting of ULBP2, ULPB1, ULBP3, ULBP4, ULBP5 and ULBP6. 
     
     
         6 . The beta-herpesvirus according to  claim 4 , wherein the MHC class-1-related protein is selected from the group consisting of MICA and MICB. 
     
     
         7 . The beta-herpesvirus according to  claim 1 , wherein the beta-herpesvirus is suitable for inducing an immune response against a beta-herpesvirus, wherein the immune response comprises neutralizing antibodies against beta-herpesvirus and/or CD4 +  T-cells directed against epitopes of beta-herpesvirus and/or CD8 +  T-cells directed against epitopes of beta-herpesvirus. 
     
     
         8 . The beta-herpesvirus according to  claim 1 , wherein the beta-herpesvirus is human cytomegalovirus. 
     
     
         9 . The beta-herpesvirus of  claim 1 , wherein the beta-herpesvirus is deficient in at least one gene product encoded by an immune modulatory gene. 
     
     
         10 . The beta-herpesvirus according to  claim 9 , wherein the at least one immune modulatory gene is selected from the group consisting of UL16 and UL142. 
     
     
         11 . The beta-herpesvirus according to  claim 9 , wherein the beta-herpesvirus is deficient in one or more additional gene product(s) each encoded by an additional immune modulatory gene. 
     
     
         12 . The beta-herpesvirus according to  claim 11 , wherein the at least one additional gene product encoded by the additional immune modulatory gene is a gene product regulating NK cell response encoded by an immune modulatory gene selected from the group consisting of UL16, UL18, UL40, UL142, m152, m155, m145 and m138. 
     
     
         13 . The beta-herpesvirus of  claim 11 , wherein the at least one additional gene product encoded by the additional immune modulatory gene is a gene product regulating MHC class I presentation, wherein the gene product regulating MHC class I presentation is a gene product encoded by an immune modulatory gene selected from the group consisting of US6, US3, US2 and US11. 
     
     
         14 . The beta-herpesvirus according to  claim 1 , wherein the beta-herpesvirus comprises the deletion of at least one miRNA. 
     
     
         15 . The beta-herpesvirus according to  claim 1 , wherein the beta-herpesvirus is deficient in at least one gene product encoded by a gene regulating viral replication, wherein the gene regulating viral replication is selected from the group consisting of IE1, pp 71 and pp65. 
     
     
         16 . The beta-herpesvirus according to  claim 1 , wherein the beta-herpesvirus is deficient in at least one gene product encoded by an essential gene, wherein the essential gene is selected from the group consisting of UL32, UL34, UL37.1, UL44, UL46, UL48, UL48, UL49, UL50, UL51, UL52, UL53, UL54, UL55, UL56, UL57, UL60, UL70, UL71, UL73, UL75, UL76, UL77, UL79, UL80, UL84, UL85, UL86, UL87, UL89.1, UL90, UL91, UL92, UL93, UL94, UL95, UL96, UL98, UL99, UL100, UL102, UL104, UL105, UL115 and UL122. 
     
     
         17 . The beta-herpesvirus according to  claim 1 , wherein the beta-herpesvirus is deficient in at least one glycoprotein. 
     
     
         18 . The beta-herpesvirus according to  claim 1 , wherein the beta-herpesvirus encodes at least one additional heterologous nucleic acid. 
     
     
         19 . The beta-herpesvirus according to  claim 18 , wherein the at least one additional heterologous nucleic acid is a functional nucleic acid selected from the group consisting of antisense molecules, ribozymes and RNA interference mediating nucleic acids or wherein the at least one additional heterologous nucleic acid is a heterologous nucleic acid coding for a peptide, oligopeptide, polypeptide or protein. 
     
     
         20 . The beta-herpesvirus according to  claim 19 , wherein the peptide, oligopeptide, polypeptide or protein constitutes or comprises at least one antigen, wherein the antigen is an antigen selected from the group consisting of tumor antigens, tumor associated antigens, viral antigens, bacterial antigens and parasite antigens. 
     
     
         21 . The beta-herpesvirus according to  claim 20 , wherein the viral antigen is an antigen derived from a virus, wherein the virus is selected from the group consisting of HIV, Influenza, HPV and RSV. 
     
     
         22 . The beta-herpesvirus according to  claim 20 , wherein the bacterial antigen is an antigen derived from a bacterium, wherein the bacterium is selected from the group consisting of mycobacterium,  Helicobacter pylori  and  Listeria.    
     
     
         23 . The beta-herpesvirus according to  claim 20 , wherein the parasite antigen is an antigen derived from a parasite, wherein the parasite is selected from the group consisting of  Plasmodium.    
     
     
         24 . A method for the treatment or prevention of a disease comprising administering to a subject the beta-herpesvirus according to  claim 1 . 
     
     
         25 . The method according to  claim 24 , wherein the disease is a disease or condition which is associated with beta-herpesvirus infection. 
     
     
         26 . The method according to  claim 24 , wherein the disease is a disease selected from the group consisting of bacterial disease, viral disease, parasite disease and tumors, wherein the beta-herpesvirus is expressing a bacterial antigen, a viral antigen, a parasite antigen or a tumor antigen. 
     
     
         27 . A method for the vaccination of a subject against a diseases, comprising the administration to the subject of the beta-herpesvirus according to  claim 1 . 
     
     
         28 . A nucleic acid coding for a beta-herpesvirus as defined in  claim 1 . 
     
     
         29 . An expression vector, comprising the nucleic acid according to  claim 28 . 
     
     
         30 . A pharmaceutical composition comprising a beta-herpesvirus according to  claim 1  and/or a nucleic acid according to  claim 28 , and a pharmaceutically acceptable carrier.