Recombinant mumps virus vaccine

Patent metadata

Field	Value
Publication number	US-9649371-B2
Application number	US-201214001228-A
Country	US
Kind code	B2
Filing date	Feb 24, 2012
Priority date	Feb 25, 2011
Publication date	May 16, 2017
Grant date	May 16, 2017

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 MuV 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).

First claim

What is claimed is:

1. An isolated nucleotide sequence comprising a cDNA sequence encoding the full length RNA genome of a mumps virus, wherein the cDNA sequence encoding the full length RNA genome of the mumps virus comprises one or more mutations to the V/I/P gene abrogating expression of a V protein product, wherein the mumps virus is an infectious mumps virus, wherein the one or more mutations to the V/I/P gene abrogating expression of the V protein comprise replacing the nucleotide sequence GGGGGG with the nucleotide sequence GAGGAGGG at the editing site in the P/V gene, wherein only a transcript encoding the P protein is generated from the P/V transcript.

2. The isolated nucleotide sequence of claim 1 , the cDNA sequence encoding the full length RNA genome of a mumps virus further 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 of claim 1 further comprising a mutation and/or deletion in the cDNA sequence encoding the full length RNA genome of a mumps virus.

4. The isolated nucleotide sequence of claim 3 wherein the mutation or deletion effects phosphorylation of the P protein of the mumps virus.

5. The isolated nucleotide sequence claim 3 comprising a mutation of the L gene of the mumps virus.

6. The isolated nucleotide sequence of claim 1 wherein the nucleotide sequence expresses an I protein product.

7. The isolated nucleotide sequence of claim 1 wherein the mumps virus is MuV/lowaUS/2006 (MuV-IA).

8. A recombinant mumps virus (rMuV) comprising a full-length genome comprising a sequence equivalent to the cDNA sequence of claim 1 .

9. A plasmid comprising the isolated nucleotide sequence of claim 1 .

10. 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 of claim 1 to the subject.

11. A method of vaccinating a subject against mumps, the method comprising administering an effective amount of an isolated nucleotide sequence of claim 1 to the subject.

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 virus 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 further comprising the deletion of 156 nucleotides of the ORF encoding the SH protein.

14. The isolated nucleotide sequence comprising the cDNA sequence encoding the full length RNA genome of a mumps virus of claim 1 further comprising the addition of four nucleotides to the 3′ untranslated region of the transcript encoding the P protein.

15. 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 genotype A or genotype G.

16. A composition comprising an isolated nucleotide acid sequence of claim 1 .

17. The isolated nucleotide sequence of claim 7 , wherein the cDNA sequence encoding the full length RNA genome of the MuV/IowaUS/2006 (MuV-IA) virus comprises SEQ ID NO:1.

18. An infectious recombinant mumps virus (rMuV) comprising a full-length genome comprising a sequence equivalent to the cDNA sequence of claim 1 .

19. A method of inducing an immune response to mumps virus in a subject, the method comprising administering an effective amount of a recombinant mumps virus (rMuV) of claim 18 to the subject.

20. An infectious recombinant mumps virus (rMuV) comprising a full-length genome comprising a sequence equivalent to the cDNA sequence of claim 2 .

21. A method of inducing an immune response to mumps virus in a subject, the method comprising administering an effective amount of a recombinant mumps virus (rMuV) of claim 20 to the subject.

22. The isolated nucleotide sequence of claim 3 comprising a mutation encoding amino acid residue 147 and/or amino acid residue 307 of the P protein.

23. A composition comprising an infectious viral particle of claim 18 .

24. The composition of claim 23 further comprising a rubella and/or measles antigenic determinant.

Assignees

• He Biao
• Univ Georgia

Inventors

• He Biao

Classifications

• A61K2039/543

  intranasal · CPC title

• A61K39/165 Primary

  Mumps or measles virus · CPC title

• C12N7/00

  Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title

• A61K2039/5256

  expressing foreign proteins · CPC title