Recombinant Viral Vectors and Methods for Inducing an Immune Response to Yellow Fever Virus

• US 20120328649A1
• Filed: 09/22/2011
• Published: 12/27/2012
• Est. Priority Date: 09/23/2010
• Status: Abandoned Application

• Current Assignee: Baxter Healthcare SA (Baxter International Inc.), Baxter International Inc.
• Original Assignee: Baxter Healthcare SA (Baxter International Inc.), Baxter International Inc.
• Inventors: Barrett, P. Noel, Falkner, Falko-Günter, Schäfer, Birgit, Holzer, Georg, Ehrlich, Hartmut
• Application Number:
  US13/240,794
• Publication Number:
  US 20120328649A1
• Time in Patent Office: Days
• US Class Current: 424/199.1
• CPC Class Codes: A61K 2039/5256 expressing foreign proteins
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C12N 15/86 Viral vectors
• CPC Class Codes: C12N 2710/24143 viral genome or elements thereof as genetic vector
• CPC Class Codes: C12N 2770/24134 Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention relates to recombinant viral vectors and methods of using the recombinant viral vectors to induce an immune response to yellow fever virus. The invention provides recombinant viral vectors based on the non-replicating modified vaccinia virus Ankara or based on a D4R-defective vaccinia virus. When administered according to methods of the invention, the recombinant viral vectors induce a broad immune response to yellow fever virus and demonstrate an excellent safety profile.

Claims

1. A recombinant, modified vaccinia virus Ankara (MVA) comprising a gene cassette encoding a yellow fever virus (YFV) prME polypeptide.

2. The recombinant MVA of claim 1 wherein the gene cassette encodes a YFV prME amino acid sequence set out in SEQ ID NO:

2, SEQ ID NO;

5, SEQ ID NO;

6, SEQ ID NO;

7, SEQ ID NO;

8, SEQ ID NO;

9, or SEQ ID NO;

10.

3. The recombinant MVA of claim 1 wherein expression of the YFV prME polypeptide from the gene cassette is under the control of an mH5 promoter or selP promoter.

5. The recombinant MVA of claim 1 comprising the YFV-17D prME gene cassette set out in SEQ ID NO:

1.

6. The recombinant MVA of claim 1 comprising the YFV-17D prME gene cassette set out in SEQ ID NO:

3.

7. The recombinant MVA of claim 1 wherein the prME gene cassette is inserted in the MVA in the deletion I region, the deletion II region, the deletion III region, the deletion IV region, the thymidine kinase locus, the D4/5 intergenic region, or the HA locus.

4. (canceled)

8-12. -12. (canceled)

13. A pharmaceutical composition comprising a recombinant, modified vaccinia virus Ankara (MVA) comprising a gene cassette encoding a yellow fever virus (YFV) prME polypeptide.

14. The pharmaceutical composition of claim 13 wherein the gene cassette encodes a YFV prME amino acid sequence set out in SEQ ID NO:

2, SEQ ID NO;

5, SEQ ID NO;

6, SEQ ID NO;

7, SEQ ID NO;

8, SEQ ID NO;

9, or SEQ ID NO;

10.

15. The pharmaceutical composition of claim 13 wherein expression of the YFV prME polypeptide from the gene cassette is under the control of an mH5 promoter or selP promoter.

17. The pharmaceutical composition of claim 13 comprising the YFV-17D prME gene cassette set out in SEQ ID NO:

1.

18. The pharmaceutical composition of claim 13 comprising the YFV-17D prME gene cassette set out in SEQ ID NO:

3.

19. The pharmaceutical composition of claim 13 wherein the prME gene cassette is inserted in the MVA in the deletion I region, the deletion II region, the deletion III region, the deletion IV region, the thymidine kinase locus, the D4/5 intergenic region, or the HA locus.

16. (canceled)

20-24. -24. (canceled)

25. A method of inducing an immune response to YFV in an individual comprising administering to the individual a pharmaceutical composition comprising a recombinant, modified vaccinia virus Ankara (MVA) comprising a gene cassette encoding a yellow fever virus (YFV) prME polypeptide.

26. The method of claim 25 wherein the gene cassette encodes a YFV prME amino acid sequence set out in SEQ ID NO:

2, SEQ ID NO;

5, SEQ ID NO;

6, SEQ ID NO;

7, SEQ ID NO;

8, SEQ ID NO;

9, or SEQ ID NO;

10.

27. The method of claim 25 wherein expression of the YFV prME polypeptide from the gene cassette is under the control of an mH5 promoter or selP promoter.

29. The method of claim 25 of inducing an immune response to YFV in an individual comprising administering to the individual a pharmaceutical composition comprising the YFV-17D prME gene cassette set out in SEQ ID NO:

1.

30. The method of claim 25 of inducing an immune response to YFV in an individual comprising administering to the individual a pharmaceutical composition comprising the YFV-17D prME gene cassette set out in SEQ ID NO:

3.

31. The method of claim 25 wherein the prME gene cassette is inserted in the MVA in the deletion I region, the deletion II region, the deletion III region, the deletion IV region, the thymidine kinase locus, the D4/5 intergenic region, or the HA locus.

37. The method of claim 25, wherein the pharmaceutical composition is administered as a single dose.

28. (canceled)

32-36. -36. (canceled)

38-74. -74. (canceled)