Recombinant Parainfluenza Virus Expression Systems And Vaccines

Abstract

The present invention relates to recombinant bovine parainfluenza virus (bPIV) cDNA or RNA which may be used to express heterologous gene products in appropriate host cell systems and/or to rescue negative strand RNA recombinant viruses that express, package, and/or present the heterologous gene product. The chimeric viruses and expression products may advantageously be used in vaccine formulations including vaccines against a broad range of pathogens and antigens.

1 . A chimeric parainfluenza virus comprising a backbone encoded by nucleotide sequences derived from a Kansas-strain bovine parainfluenza virus type 3 genome in which Kansas-strain bPIV3 nucleotide sequences have been. substituted with heterologous sequences or in which heterologous sequences have been added to the complete Kansas strain bPIV3 genome. 
     
     
         2 - 11 . (canceled) 
     
     
         12 . A vaccine formulation comprising a chimeric Kansas: —strain bPIV3, the genome of which encodes a heterologous epitope, and a pharmaceutically acceptable excipient. 
     
     
         13 . The vaccine formulation of  claim 12 , comprising genomic modifications or mutations which result in an attenuated phenotype or enhanced antigenicity. 
     
     
         14 . The vaccine formulation of  claim 13  in which the modification is derived from a naturally occurring mutant. 
     
     
         15 . The vaccine formulation of  claim 12  wherein the vaccine is used to modulate the immune response of humans, primates, horses, cows, sheep, pigs, goats, dogs, cats, avian species and rodents. 
     
     
         16 . The vaccine formulation of  claim 15 , wherein the vaccine is used to modulate the immune response of human infants and children. 
     
     
         17 . A vaccine formulation comprising a recombinant parainfluenza virus having a genome wherein the polymerase (L) gene encodes a naturally occurring amino acid residue at position 1103 which is selected from the group consisting of: glycine, alanine, valine, phenylalanine, tyrosine, tryptophan, methionine, cysteine, serine, threonine, arginine, lysine, histidine, proline, glutamate, aspartate, glutamine, and asparagine, and a pharmaceutically acceptable excipient. 
     
     
         18 . The recombinant parainfluenza virus of  claim 17  wherein position 1103 of the L gene is valine. 
     
     
         19 . A recombinant parainfluenza virus of  claim 17  having a genome which comprises a heterologous gene selected from the group consisting of: bPIV1 FIN, hPIV2 HN, bPIV3 FIN, bPIV1 FIN, bPIV2 FIN, bPIV1 F, hPIV2 F, hPIV3 F, bPIV1 F, bPIV2 F, RSV (Type A) F, RSV (Type B) F, RSV (Type A) G, and RSV (Type B) G. 
     
     
         20 . (canceled) 
     
     
         21 . A method of vaccinating a patient comprising administering to a patient an efficacious dose of the vaccine composition of  claim 12 . 
     
     
         22 . (canceled) 
     
     
         23 . A method of vaccinating a patient comprising administering to a patient an efficacious dose of the vaccine composition  claim 17 .