Attenuated parainfluenza virus (PIV) vaccines
AssigneeGovernment of the US, as represented by the Secretary, Dept. of Health and Human Services
InventorsBrian Murphy, Peter Collins, Anna Durbin, Mario Skiadopoulos, Tao Tao, Alexander Schmidt, Jane Bailly
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Abstract
The invention provides isolated nucleic acids encoding recombinant genomes or antigenomes of Human Parainfluenza Viruses that are useful as vaccines. The recombinant genomes or antigenomes can be incorporated into expression vectors for production of recombinant viruses in vitro. The invention also provides recombinant Human Parainfluenza viruses having one or more mutations that attenuate replication of the virus in a host.
Claims8
An isolated polynucleotide molecule comprising an operably linked
- i) transcriptional promoter operative in a mammalian cell or operative in vitro;
- ii) a polynucleotide sequence encoding a partial or complete human PIV genome or antigenome that encodes at least a nucleocapsid (N) protein, a nucleocapsid phosphoprotein (P) and a large polymerase (L) protein of a human PIV and that includes at least one mutation at a position corresponding to a position in the genome of HPIV3 selected from the group consisting of Val96 of the N protein, Ser389 of the N protein, Ile96 of the C protein, Pro199 of the M protein, Ile420 of the F protein, Ala450 of the F protein, Val384 of the HN protein, nucleotide 23 of the 3′ leader sequence, nucleotide 24 of the 3′ leader sequence, nucleotide 28 of the 3′ leader sequence, nucleotide 45 of the 3′ leader sequence and nucleotide 62 in the N gene start sequence;
- iii) a polynucleotide sequence encoding a ribozyme, that is located flanking the polynucleotide ii) at the 5′ trailer end of the polynucleotide, and
- iv) a transcriptional terminator operative in a mammalian cell or operative in vitro.
An isolated polynucleotide molecule comprising an operably linked
- i) transcriptional promoter operative in a mammalian cell or operative in vitro;
- ii) a polynucleotide sequence encoding a partial or complete human PIV genome or antigenome that encodes at least a nucleocapsid (N) protein, a nucleocapsid phosphoprotein (P) and a large polymerase (L) protein of a human PIV and that includes a mutation at the amino acid corresponding to Phe456 of the L protein of HPIV3 and at least one mutation at a position corresponding to a position in the genome of HPIV3 selected from the group consisting of Val96 of the N protein, Ser389 of the N protein, Ile96 of the C protein, Pro199 of the M protein, Ile420 of the F protein, Ala450 of the F protein, Val384 of the HN protein, nucleotide 23 of the 3′ leader sequence, nucleotide 24 of the 3′ leader sequence, nucleotide 28 of the 3′ leader sequence, nucleotide 45 of the 3′ leader sequence and nucleotide 62 in the N gene start sequence;
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- iii) a transcriptional terminator operative in a mammalian cell or operative in vitro.
An infectious, attenuated parainfluenza virus the comprises a genome or antigenome that encodes at least a nucleocapsid (N) protein, a nucleocapsid phosphoprotein (P) and a large polymerase (L) protein of a human PIV and that includes a mutation at the amino acid corresponding to Phe456 of the L protein of HPIV3 and at least one mutation at a position corresponding to a position in the genome of HPIV3 selected from the group consisting of Val96 of the N protein, Ser389 of the N protein, Ile96 of the C protein, Pro199 of the M protein, Ile420 of the F protein, Ala450 of the F protein, Val384 of the HN protein, nucleotide 23 of the 3′ leader sequence, nucleotide 24 of the 3′ leader sequence, nucleotide 28 of the 3′ leader sequence, nucleotide 45 of the 3′ leader sequence and nucleotide 62 in the N gene start sequence.
Dependencies are inferred from the claim text.