IP Library › Granted Patent US 10,098,945

Granted Patent B2

US 10,098,945 · App. 15/375,664 · Granted Oct 16, 2018

Genetically engineered swine influenza virus and uses thereof

Inventors: Peter Palese (New York, NY); Adolfo Garcia-Sastre (New York, NY); Richard J. Webby (Memphis, TN); Juergen A. Richt (Ames, IA); Robert G. Webster (Memphis, TN); Kelly M. Lager (Colo, IA)

Assignees: Icahn School of Medicine at Mount Sinai; St. Jude Children's Research Hospital; The United States of America, As Represented by the Secretary of Agriculture

A61K39/145 C12N7/00 A61K2039/5254 A61K2039/5256 A61K2039/552 C12N2760/16034 C12N2760/16121 C12N2760/16171

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Quick Facts

Patent No.: US 10,098,945
App. No.: 15/375,664
Granted: Oct 16, 2018
Kind: B2

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Abstract

The present invention relates, in general, to attenuated swine influenza viruses having an impaired ability to antagonize the cellular interferon (IFN) response, and the use of such attenuated viruses in vaccine and pharmaceutical formulations. In particular, the invention relates to attenuated swine influenza viruses having modifications to a swine NS1 gene that diminish or eliminate the ability of the NS1 gene product to antagonize the cellular IFN response. These viruses replicate in vivo, but demonstrate decreased replication, virulence and increased attenuation, and therefore are well suited for use in live virus vaccines, and pharmaceutical formulations.

Claims (34)

1. A method for preventing swine influenza virus disease in a pig, comprising administering to the pig an effective amount of an immunogenic composition comprising a genetically engineered attenuated swine influenza virus having an impaired interferon antagonist phenotype, wherein the virus comprises a swine influenza virus NS1 gene with a mutation resulting in a swine influenza virus NS1 protein having a deletion of between 90 and 94 amino acid residues from the carboxy-terminus of NS1.

2. The method of claim 1 , wherein the swine influenza virus NS1 gene is from A/Swine/Texas/4199-2/98.

3. The method of claim 1 , wherein the genetically engineered attenuated swine influenza virus is A/Swine/Texas/4199-2/98.

4. The method of claim 1 , wherein the NS1 amino acids are counted on the basis of A/Swine/Texas/4199-2/98.

5. The method of claim 1 , wherein the swine influenza virus is H1N1, H1N2, H3N2, H3N1, H9N2, or H5N1.

6. The method of claim 1 , wherein the attenuated virus is a reassortant.

7. The method of claim 1 , wherein the attenuated virus is a chimeric virus comprising a heterologous sequence.

8. The method of claim 1 , wherein the attenuated virus is a chimeric virus that expresses an epitope of a foreign pathogen.

9. The method of claim 1 , wherein the attenuated virus is engineered to express an epitope from a different virus or at least one segment derived from a different virus.

10. The method of claim 1 , wherein the virus comprises a swine influenza virus NS1 gene with a mutation resulting in a swine influenza virus NS1 protein having a deletion of 90 amino acid residues from the carboxy-terminus of NS1.

11. The method of claim 10 , wherein the swine influenza virus NS1 gene is from A/Swine/Texas/4199-2/98.

12. The method of claim 10 , wherein the genetically engineered attenuated swine influenza virus is A/Swine/Texas/4199-2/98.

13. The method of claim 10 , wherein the NS1 amino acids are counted on the basis of A/Swine/Texas/4199-2/98.

14. The method of claim 10 , wherein the swine influenza virus is H1N1, H1N2, H3N2, H3N1, H9N2, or H5N1.

15. The method of claim 10 , wherein the attenuated virus is a reassortant.

16. The method of claim 10 , wherein the attenuated virus is a chimeric virus comprising a heterologous sequence.

17. The method of claim 10 , wherein the attenuated virus is a chimeric virus that expresses an epitope of a foreign pathogen.

18. The method of claim 10 , wherein the attenuated virus is engineered to express an epitope from a different virus or at least one segment derived from a different virus.

19. The method of claim 1 , wherein said mutation in a swine influenza NS1 gene is in an NS1 gene from A/Swine/Colorado/1/77, A/Swine/Colorado/23619/99, A/Swine/Cote d'Armor/3633/84, A/Swine/Cote d'Armor/3633/84, A/Swine/England/195852/92, A/Swine/Finistere/2899/82, A/Swine/Hong Kong/10/98, A/Swine/Hong Kong/9/98, A/Swine/Hong Kong/81/78, A/Swine/Illinois/100084/01, A/Swine/Illinois/100085A/01, A/Swine/Illinois/21587/99, A/Swine/Indiana/1726/88, A/Swine/Indiana/9K035/99, A/Swine/Indiana/P12439/00, A/Swine/Iowa/30, A/Swine/Iowa/15/30, A/Swine/Iowa/533/99, A/Swine/Iowa/569/99, A/Swine/Iowa/3421/90, A/Swine/Iowa/8548-1/98, A/Swine/Iowa/930/01, A/Swine/Iowa/17672/88, A/Swine/Italy/1513-1/98, A/Swine/Italy/1523/98, A/Swine/Korea/CY02/02, A/Swine/Minnesota/55551/00, A/Swine/Minnesota/593/99, A/Swine/Minnesota/9088-2/98, A/Swine/Nebraska/1/92, A/Swine/Nebraska/209/98, A/Swine/Netherlands/12/85, A/Swine/North Carolina/16497/99, A/Swine/North Carolina/35922/98, A/Swine/North Carolina/93523/01, A/Swine/North Carolina/98225/01, A/Swine/Oedenrode/7C/96, A/Swine/Ohio/891/01, A/Swine/Oklahoma/18717/99, A/Swine/Oklahoma/18089/99, A/Swine/Ontario/01911-1/99, A/Swine/Ontario/01911-2/99, A/Swine/Ontario/41848/97, A/Swine/Ontario/97, A/Swine/Quebec/192/81, A/Swine/Quebec/192/91, A/Swine/Quebec/5393/91, A/Swine/Taiwan/7310/70, A/Swine/Tennessee/24/77, A/Swine/Texas/4199-2/98, A/Swine/Wisconsin/125/97, A/Swine/Wisconsin/136/97, A/Swine/Wisconsin/163/97, A/Swine/Wisconsin/164/97, A/Swine/Wisconsin/166/97, A/Swine/Wisconsin/168/97, A/Swine/Wisconsin/235/97, A/Swine/Wisconsin/238/97, A/Swine/Wisconsin/457/98, A/Swine/Wisconsin/458/98, A/Swine/Wisconsin/464/98 or A/Swine/Wisconsin/14094/99 swine influenza virus.

20. The method of claim 10 , wherein said mutation in a swine influenza NS1 gene is in an NS1 gene from A/Swine/Colorado/1/77, A/Swine/Colorado/23619/99, A/Swine/Cote d'Armor/3633/84, A/Swine/Cote d'Armor/3633/84, A/Swine/England/195852/92, A/Swine/Finistere/2899/82, A/Swine/Hong Kong/10/98, A/Swine/Hong Kong/9/98, A/Swine/Hong Kong/81/78, A/Swine/Illinois/100084/01, A/Swine/Illinois/100085A/01, A/Swine/Illinois/21587/99, A/Swine/Indiana/1726/88, A/Swine/Indiana/9K035/99, A/Swine/Indiana/P12439/00, A/Swine/Iowa/30, A/Swine/Iowa/15/30, A/Swine/Iowa/533/99, A/Swine/Iowa/569/99, A/Swine/Iowa/3421/90, A/Swine/Iowa/8548-1/98, A/Swine/Iowa/930/01, A/Swine/Iowa/17672/88, A/Swine/Italy/1513-1/98, A/Swine/Italy/1523/98, A/Swine/Korea/CY02/02, A/Swine/Minnesota/55551/00, A/Swine/Minnesota/593/99, A/Swine/Minnesota/9088-2/98, A/Swine/Nebraska/1/92, A/Swine/Nebraska/209/98, A/Swine/Netherlands/12/85, A/Swine/North Carolina/16497/99, A/Swine/North Carolina/35922/98, A/Swine/North Carolina/93523/01, A/Swine/North Carolina/98225/01, A/Swine/Oedenrode/7C/96, A/Swine/Ohio/891/01, A/Swine/Oklahoma/18717/99, A/Swine/Oklahoma/18089/99, A/Swine/Ontario/01911-1/99, A/Swine/Ontario/01911-2/99, A/Swine/Ontario/41848/97, A/Swine/Ontario/97, A/Swine/Quebec/192/81, A/Swine/Quebec/192/91, A/Swine/Quebec/5393/91, A/Swine/Taiwan/7310/70, A/Swine/Tennessee/24/77, A/Swine/Texas/4199-2/98, A/Swine/Wisconsin/125/97, A/Swine/Wisconsin/136/97, A/Swine/Wisconsin/163/97, A/Swine/Wisconsin/164/97, A/Swine/Wisconsin/166/97, A/Swine/Wisconsin/168/97, A/Swine/Wisconsin/235/97, A/Swine/Wisconsin/238/97, A/Swine/Wisconsin/457/98, A/Swine/Wisconsin/458/98, A/Swine/Wisconsin/464/98 or A/Swine/Wisconsin/14094/99 swine influenza virus.

21. A method for immunizing a pig in need thereof against swine influenza virus, comprising administering to the pig an effective amount of an immunogenic composition comprising a genetically engineered attenuated swine influenza virus having an impaired interferon antagonist phenotype, wherein the virus comprises a swine influenza virus NS1 gene with a mutation resulting in a swine influenza virus NS1 protein having a deletion of between 90 and 94 amino acid residues from the carboxy-terminus of NS1.

22. A method for immunizing a pig in need thereof against swine influenza virus, comprising administering to the pig an effective amount of an immunogenic composition comprising a genetically engineered attenuated swine influenza virus having an impaired interferon antagonist phenotype, wherein the virus comprises a swine influenza virus NS1 gene with a mutation resulting in a swine influenza virus NS1 protein having a deletion of 90 amino acid residues from the carboxy-terminus of NS1.

23. The method of claim 21 , wherein the swine influenza virus NS1 gene is from A/Swine/Texas/4199-2/98.

24. The method of claim 21 , wherein the genetically engineered attenuated swine influenza virus is A/Swine/Texas/4199-2/98.

25. The method of claim 21 , wherein the NS1 amino acids are counted on the basis of A/Swine/Texas/4199-2/98.

26. The method of claim 21 , wherein the attenuated virus is a chimeric virus comprising a heterologous sequence.

27. The method of claim 21 , wherein the attenuated virus is a chimeric virus that expresses an epitope of a foreign pathogen.

28. The method of claim 21 , wherein the attenuated virus is engineered to express an epitope from a different virus or at least one segment derived from a different virus.

29. The method of claim 22 , wherein the swine influenza virus NS1 gene is from A/Swine/Texas/4199-2/98.

30. The method of claim 22 , wherein the genetically engineered attenuated swine influenza virus is A/Swine/Texas/4199-2/98.

31. The method of claim 22 , wherein the NS1 amino acids are counted on the basis of A/Swine/Texas/4199-2/98.

32. The method of claim 22 , wherein the attenuated virus is a chimeric virus comprising a heterologous sequence.

33. The method of claim 22 , wherein the attenuated virus is a chimeric virus that expresses an epitope of a foreign pathogen.

34. The method of claim 22 , wherein the attenuated virus is engineered to express an epitope from a different virus or at least one segment derived from a different virus.

Assignments (5)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 25, 2018

From: WEBBY, RICHARD J.; WEBSTER, ROBERT G.

To: ST. JUDE CHILDREN'S RESEARCH HOSPITAL

Reel/Frame 045907/0170 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 25, 2018

From: PALESE, PETER; GARCIA-SASTRE, ADOLFO

To: MOUNT SINAI SCHOOL OF MEDICINE OF NEW YORK UNIVERSITY

Reel/Frame 045907/0194 →

CHANGE OF NAME Recorded May 25, 2018

From: MOUNT SINAI SCHOOL OF MEDICINE OF NEW YORK UNIVERSITY

To: MOUNT SINAI SCHOOL OF MEDICINE