Recombinant mumps virus vaccine

Abstract

The present invention provides the complete genomic sequence of the epidemic mumps virus (MuV) strain MuV Iowa/US/06 . Further, a reverse genetics system was constructed and used to rescue recombinant viral constructs that are attenuated compared to rMuV Iowa/US/06 and JL vaccine viruses. Such constructs include viral constructs lacking the open reading frame (ORF) of the SH gene (rMuVΔSH) and/or incapable of expressing the V protein (rMuVΔV).

What is claimed is: 
     
         1 . An isolated nucleotide sequence comprising the cDNA sequence encoding the full length RNA genome of a mumps virus, wherein the isolated nucleotide sequence encodes a mumps virus unable to express a small hydrophobic (SH) protein product and/or express a V protein product. 
     
     
         2 . The isolated nucleotide sequence comprising the cDNA sequence encoding the full length RNA genome of a mumps virus of  claim 1  comprising a deletion of the open reading frame (ORF) encoding the SH protein, a mutation converting a start codon into a stop codon, or a mutation in the region between the ORF encoding the F polypeptide and the ORF encoding the SH polypeptide that disrupts transcription of the SH gene. 
     
     
         3 . The isolated nucleotide sequence comprising the cDNA sequence encoding the full length RNA genome of a mumps virus of  claim 2  comprising a deletion of the ORF encoding the SH protein. 
     
     
         4 . The isolated nucleotide sequence comprising the cDNA sequence encoding the full length RNA genome of a mumps virus of  claim 3  comprising a deletion of 156 nucleotides of the ORF encoding the SH protein. 
     
     
         5 . The isolated nucleotide sequence comprising the cDNA sequence encoding the full length RNA genome of a mumps virus of  claim 1  comprising one or more mutations to the V/I/P gene abrogating expression of the V protein. 
     
     
         6 . The isolated nucleotide sequence comprising the cDNA sequence encoding the full length RNA genome of a mumps virus of  claim 1  comprising:
 a deletion of the open reading frame (ORF) encoding the SH protein, a mutation converting a start codon into a stop codon, or a mutation in the region between the ORF encoding the F polypeptide and the ORF encoding the SH polypeptide that disrupts transcription of the SH gene; and 
 one or more mutations to the V/I/P gene abrogating expression of the V protein. 
 
     
     
         7 . The isolated nucleotide sequence comprising the cDNA sequence encoding the full length RNA genome of a mumps virus of  claim 6  wherein the one or more mutations to the V/I/P gene abrogating expression of the V protein comprise the nucleotide sequence GAGGAGGG at the editing site in the P/V gene. 
     
     
         8 . The isolated nucleotide sequence comprising the cDNA sequence encoding the full length RNA genome of a mumps virus of  claim 1  comprising a further mutation and/or deletion. 
     
     
         9 . The isolated nucleotide sequence comprising the cDNA sequence encoding the full length RNA genome of a mumps virus of  claim 8  comprising a mutation or deletion effecting phosphorylation of the P protein. 
     
     
         10 . The isolated nucleotide sequence comprising the cDNA sequence encoding the full length RNA genome of a mumps virus of  claim 1  further comprising a mutation of the L gene. 
     
     
         11 . The isolated nucleotide sequence comprising the cDNA sequence encoding the full length RNA genome of a mumps virus of  claim 1  further comprising expression of an I protein product. 
     
     
         12 . The isolated nucleotide sequence comprising the cDNA sequence encoding the full length RNA genome of a mumps virus of  claim 1 , wherein the mumps genome further encodes a heterologous polypeptide. 
     
     
         13 . The isolated nucleotide sequence comprising the cDNA sequence encoding the full length RNA genome of a mumps virus of  claim 1  wherein the mumps virus is MuV/IowaUS/2006 (MuV-IA). 
     
     
         14 . A recombinant mumps virus (rMuV) or plasmid encoding a measles virus genome (pMuV) comprising an isolated nucleotide acid sequence of  claim 1 . 
     
     
         15 . A plasmid comprising the isolated nucleotide sequence of  claim 1 , or a fragment thereof. 
     
     
         16 . A method of inducing an immune response to mumps virus in a subject, the method comprising administering an effective amount of an isolated nucleotide sequence plasmid, pMuV, rMuV, viral particle, or composition of  claim 1  to the subject. 
     
     
         17 . A method of vaccinating a subject against mumps, the method comprising administering an effective amount of an isolated nucleotide sequence plasmid, pMuV, rMuV, viral particle, or composition of  claim 1  to the subject.