Cmv glycoproteins and recombinant vectors

Abstract

This invention also relates to recombinant vectors expressing one or more of the human CMV (HCMV) glycoproteins US2, US3, US6 and US11 or corresponding functional rhesus CMV (RhCMV) homologues Rh182, Rh184, Rh185 or Rh189, methods of making them, uses for them, expression products from them, and uses for the expression products. This invention also relates to recombinant cytomegalovirus vectors vectors lacking one or more of the glycoproteins, methods of making them, uses for them, expression products from them, and uses for the expression products.

What is claimed is: 
     
         1 . A method to enable superinfection or repeated infection of an animal by a vector containing and expressing at least one cytomegalovirus (CMV) glycoprotein, wherein the glycoprotein is US2, US3, US6 or US11 of human CMV (HCMV) or the corresponding functional homologues Rh182, Rh184, Rh185 or Rh189 of rhesus CMV (RhCMV), and administering the vector into the animal, wherein the vector expresses at least one cytomegalovirus glycoprotein. 
     
     
         2 . The method of  claim 1 , wherein the vector is a viral vector. 
     
     
         3 . The method of  claim 2 , wherein the vector is an adenovirus vector, adeno-associated virus (AAV) vector, alphavirus vector, herpesvirus vector, retrovirus vector or poxvirus vector 
     
     
         4 . The method of  claim 1 , wherein the vector contains and expresses US2, US3, US6 and US11 of HCMV, or Rh182, Rh184, Rh185 and Rh189 of RhCMV. 
     
     
         5 . The method of  claim 1 , wherein the vector contains and expresses all of the glycoproteins within the US2 to US11 region of HCMV or Rh182 to Rh189 region of RhCMV. 
     
     
         6 . A method of determining efficacy of a CMV vaccine, comprising (a) administering a CMV vaccine to a test subject, (b) challenging the test subject with a CMV vector, wherein glycoproteins within the US2 to US11 region of CMV are deleted from the CMV vector, and wherein the CMV vector contains and expresses at least one immunogen of the CMV vaccine, and (c) measuring a CD8+ T cell response, wherein the CMV vaccine is efficacious if a CD8+ T cell response is protective against the challenge with the CMV vector lacking the glycoproteins within the US2 to US11 region of CMV and wherein the CMV vector contains and expresses at least one immunogen of the CMV vaccine. 
     
     
         7 . The method of  claim 6 , wherein the CMV vaccine lacks the transactivator pp71. 
     
     
         8 . The method of  claim 6 , wherein the CMV vaccine lacks the tegument protein pp65. 
     
     
         9 . A method of inducing a pathogen-specific CD8+ T cell response in an animal, comprising administering a CMV vector wherein the CMV vector contains and expresses at least one pathogen-derived immunogen, wherein the CD8+ T cell response in the animal confer protection against the pathogen. 
     
     
         10 . The method of  claim 9 , wherein the pathogen is a viral pathogen and the immunogen is a protein derived from the viral pathogen. 
     
     
         11 . The method of  claim 9 , wherein the pathogen is a bacterial pathogen and the immunogen is a protein derived from the bacterial pathogen. 
     
     
         12 . The method of  claim 9 , wherein the pathogen is a parasite and the immunogen is a protein derived from the parasite pathogen. 
     
     
         13 . The method of  claim 9 , wherein the pathogen is cancer and the immunogen is a protein derived from the cancer. 
     
     
         14 . A method of inducing a different pathogen-specific CD8+ T cell response in an animal, comprising administering a CMV vector with at least one cytomegalovirus (CMV) glycoprotein deleted from the CMV vector, wherein the glycoprotein is US2, US3, US6 or US11, and wherein the CMV vector contains and expresses at least one pathogen-derived immunogen, wherein the CD8+ T cell response in the animal differs as compared to a CMV vaccine with a CMV vector that contains and expresses the same immunogen and wherein a CMV glycoprotein is not deleted from the CMV vector. 
     
     
         15 . The method of  claim 14 , wherein the vector has CMV glycoproteins US2, US3, US6 and US11 deleted from the CMV vector. 
     
     
         16 . The method of  claim 14 , wherein the vector has all of the glycoproteins within the US2 to US11 region of CMV deleted from the CMV vector. 
     
     
         17 . The method of  claim 14 , wherein the pathogen is a viral pathogen and the immunogen is a protein derived from the viral pathogen. 
     
     
         18 . The method of  claim 14 , wherein the pathogen is a bacterial pathogen and the immunogen is a protein derived from the bacterial pathogen. 
     
     
         19 . The method of  claim 1 , wherein the animal is a human. 
     
     
         20 . The method of  claim 9 , wherein the animal is a human. 
     
     
         21 . The method of  claim 14 , wherein the animal is a human.