Modified Mareks Disease Virus, and Vaccines Made Therefrom

Abstract

The present invention provides an effective vaccine for Marek's disease, which may be prepared using a recombinant Marek's Disease Virus (MDV), strain CVI988, having been transformed with a foreign DNA construct that includes a long terminal repeat sequence of a reticuloendotheliosis virus. This safe viral agent elicits a highly protective immune response in a chicken against virulent MDV challenge without causing a significant degree of pathogenicity. Suitable formulations of the vaccine for use in chickens include an effective immunization dosage of this novel viral agent, along with a pharmaceutically acceptable carrier or diluent.

What is claimed is: 
     
         1 . A method of eliciting in an avian animal a safe and protective immune response against Marek's Disease virus (MDV) comprising administering to said animal a therapeutically effective amount of a composition comprising a viral agent comprising a recombinant Marek's disease virus stably transformed with a foreign DNA construct, comprising a long terminal repeat (LTR) sequence of a reticuloendotheliosis virus, thereby eliciting the protective immune response. 
     
     
         2 . The method of  claim 1  wherein the composition further comprises a veterinarily or pharmaceutically acceptable carrier or diluent. 
     
     
         3 . The method of  claim 1  or  2  wherein the MDV is a CVI988/X MDV. 
     
     
         4 . The method of  claim 3  wherein the CVI988/X MDV is CVI988. 
     
     
         5 . The method of  claim 1  or  2  wherein the avian animal is a chicken. 
     
     
         6 . The method of  claim 1  or  2  wherein the LTR is as set forth in SEQ ID NO:2. 
     
     
         7 . The method of  claim 1  or  2  wherein the LTR sequence comprises a Pac I excised-DNA segment from an MDV having all of the identifying characteristics of the strain deposited at ATCC under the accession number PTA-4945. 
     
     
         8 . The method of  claim 1  or  2  wherein the LTR sequence is inserted 5′ of the ICP4 gene of said MDV. 
     
     
         9 . The method of  claim 1  or  2  wherein the viral agent is effective to elicit an immune response in an avian against MDV without causing a significant degree of pathogenicity in said avian. 
     
     
         10 . The method of  claim 1  or  2  wherein the viral agent is cell-associated. 
     
     
         11 . A method of making a viral agent effective for protecting an avian against Marek's disease comprising transforming an MDV strain CVI988 with a foreign DNA construct which comprises a LTR sequence of a reticuloendotheliosis virus. 
     
     
         12 . A Marek's disease virus (MDV) stably transformed with a foreign DNA construct, comprising a long terminal repeat (LTR) sequence of a reticuloendotheliosis virus. 
     
     
         13 . The MDV of  claim 12  comprising a nucleotide having at least 90% homology as the sequence as set forth in SEQ ID NO:2. 
     
     
         14 . The MDV of  claim 13  wherein the nucleotide has the sequence as set forth in SEQ ID NO:2. 
     
     
         15 . An immunological composition comprising the MDV of any one of  claims 12 - 14 . 
     
     
         16 . The composition of  claim 15  wherein the MDV is a clonal virus, and not a mixed population of parental and recombinant virus. 
     
     
         17 . The composition of  claim 16  which is a vaccine composition. 
     
     
         18 . The composition of  claim 17  which provides a protection rate of at least 85%. 
     
     
         19 . The composition of  claim 18  which provides a protection rate of at least 90%. 
     
     
         20 . The composition of  claim 19  which provides a protection rate of at least 95%. 
     
     
         21 . An isolated cell stably transformed with the MDV of  claim 13  or  14 . 
     
     
         22 . The isolated cell of  claim 15 , wherein the cell is either a chicken or duck embryo fibroblast (CEF, DEF) cell.