IP Library › Granted Patent US 10,131,695
Granted Patent B2
US 10,131,695 · App. 14/345,816 · Granted Nov 20, 2018

Influenza virus vaccines and uses thereof

Inventors: Adolfo Garcia-Sastre (New York, NY); Peter Palese (New York, NY); Florian Krammer (New York, NY); Natalie Pica (New York, NY); Dirk Eggink (New York, NY); Rafael A. Medina-Silva (Santiago, CL); Rong Hai (New York, NY)
Assignee: Icahn School of Medicine at Mount Sinai
C07K14/005A61K39/12A61K39/145C12N7/00A61K2039/521A61K2039/5258A61K2039/53C07K2319/00C12N2710/14143C12N2760/16122C12N2760/16123C12N2760/16134C12N2760/16162C12N2760/16171
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Quick Facts
Patent No.
US 10,131,695
App. No.
14/345,816
Granted
Nov 20, 2018
Kind
B2
Abstract

Provided herein are flu hemagglutinin polypeptides, including chimeric influenza virus hemagglutinin polypeptides, and flu hemagglutinin polypeptides comprising modified glycosylation sites and non-naturally glycosylation sites, compositions comprising the same, vaccines comprising the same and methods of their use.

Claims (53)

1. A chimeric influenza virus hemagglutinin (HA) polypeptide comprising an HA stem domain and an HA globular head domain, wherein the HA globular head domain is from a different influenza virus subtype than the influenza virus subtype of the HA stem domain, wherein

(a) the HA stem domain comprises (i) an HA 1 N-terminal stem segment, wherein the HA 1 N-terminal stem segment consists of amino acid residues HA 1 N-term through A p ; and (ii) an HA 1 C-terminal stem segment, wherein the HA 1 C-terminal stem segment consists of amino acid residues A q through HA 1 C-term ; and

(b) the HA globular head domain comprises the amino acid residues between A p and A q of an HA 1 domain: and

wherein HA 1 N-term is the N-terminal amino acid of a mature HA 0 protein lacking a signal peptide; wherein HA 1 C-term is the C-terminal amino acid of an HA 1 domain; and wherein A p is the Cys that corresponds to amino acid position 52 of an HA 1 domain using H 3 numbering; and wherein A q is the Cys that corresponds to amino acid position 277 of an HA 1 domain using H 3 numbering.

2. The chimeric influenza virus HA polypeptide of claim 1 , wherein the HA stem domain comprises an HA2 domain, and wherein the HA stem domain is resistant to protease cleavage at the junction between HA1 and HA2.

3. The chimeric influenza virus HA polypeptide of claim 1 , wherein the chimeric influenza virus HA polypeptide is expressed and isolated from a mammalian cell.

4. The chimeric influenza virus HA polypeptide of claim 1 , wherein the chimeric influenza virus HA polypeptide is expressed and isolated from an insect cell.

5. The chimeric influenza virus HA polypeptide of claim 1 , wherein the chimeric influenza virus HA polypeptide is soluble.

6. The chimeric influenza virus HA polypeptide of claim 1 , wherein the HA stem domain is the HA stem domain of an influenza virus of subtype H1.

7. The chimeric influenza virus HA polypeptide of claim 1 , wherein the HA stem domain is the HA stem domain of an influenza virus of subtype H3.

8. An immunogenic composition comprising the chimeric influenza virus HA polypeptide of claim 1 .

9. The chimeric influenza virus HA polypeptide of claim 5 , wherein the chimeric influenza virus HA polypeptide further comprises a foldon or trimerization domain.

10. The chimeric influenza virus HA polypeptide of claim 1 , wherein the HA stem domain is from an H 1 subtype and the HA globular head domain from an H5 subtype.

11. The chimeric influenza virus HA polypeptide of claim 1 , wherein (a) the HA stem domain is from an H 1 subtype and the HA globular head domain is from an H6 subtype; or (b) the HA stem domain is from an H 1 subtype and the HA globular head domain from an H9 subtype.

12. The chimeric influenza virus HA polypeptide of claim 1 , wherein the HA stem domain is from an H3 subtype and the HA globular head domain is from an H7 subtype.

13. The chimeric influenza virus HA polypeptide of claim 1 , wherein the HA stem domain is from A/Perth/16/2009 of the H3 subtype and the HA globular head domain is from A/mallard/Alberta/24/2001 of the H7 subtype.

14. A chimeric influenza virus hemagglutinin (HA) polypeptide comprising an HA stem domain and an HA globular head domain, wherein the HA globular head domain is from a different influenza virus subtype than the influenza virus subtype of the HA stem domain, and wherein the chimeric influenza virus HA polypeptide has fusogenic activity of an influenza virus HA, wherein

(a) the HA stem domain comprises (i) an HA 1 N-terminal stem segment, wherein the HA 1 N-terminal stem seument consists of amino acid residues HA 1 N-term throuuh A p ; and (ii) an HA 1 C-terminal stem segment, wherein the HA 1 C-terminal stem segment consists of amino acid residues A q throuah HA 1 C-term ; and

(b) the HA ulobular head domain comprises the amino acid residues between A p and A q of an HA 1 domain;

wherein HA 1 N-term is the N-terminal amino acid of a mature HA 0 protein lacking a signal peptide; wherein HA 1 C-term is the C-terminal amino acid of an HA 1 domain; and wherein A p is the Cys that corresponds to amino acid position 52 of an HA 1 domain usinu H 3 numbering; and wherein A q is the Cys that corresponds to amino acid position 277 of an HA 1 domain using H3 numbering.

15. An immunogenic composition comprising the chimeric influenza virus HA polypeptide of claim 14 .

16. The chimeric influenza virus HA polypeptide of claim 1 , wherein the HA globular head domain is the HA globular head domain of an influenza virus of subtype H4, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, or H17.

17. The chimeric influenza virus HA polypeptide of claim 1 , wherein the HA globular head domain is the HA globular head domain of an influenza virus of subtype H5.

18. The chimeric influenza virus HA polypeptide of claim 1 , wherein the HA globular head domain is the HA globular head domain of an influenza virus of subtype H7.

19. The chimeric influenza virus HA polypeptide of claim 6 , wherein the H 1 subtype is A/Califomia/04/09.

20. The chimeric influenza virus HA polypeptide of claim 7 , wherein the H 3 subtype is A/Perth/16/2009.

21. The chimeric influenza virus HA polypeptide of claim 1 , wherein the HA stem domain is from an H3 subtype and the HA globular head domain from an H5 subtype.

22. The chimeric influenza virus HA polypeptide of claim 21 , wherein the H 3 subtype is A/Perth/16/2009 and the H5 subtype is A/Vietnam/1203/04.

23. The chimeric influenza virus HA polypeptide of claim 1 , wherein the HA globular head domain is from an influenza virus of subtype H4.

24. The chimeric influenza virus HA polypeptide of claim 1 , wherein the HA globular head domain is from an influenza vims of subtype H6.

25. The chimeric influenza virus HA polypeptide of claim 1 , wherein the HA globular head domain is from an influenza virus of subtype H8.

26. The chimeric influenza virus HA polypeptide of claim 1 , wherein the HA globular head domain is from an influenza virus of subtype H9.

27. The chimeric influenza virus HA polypeptide of claim 1 , wherein the HA globular head domain is from an influenza virus of subtype H10.

28. The chimeric influenza virus HA polypeptide of claim 1 , wherein the HA globular head domain is from an influenza virus of subtype H11.

29. The chimeric influenza virus HA polypeptide of claim 1 , wherein the HA globular head domain is from an influenza virus of subtype H12.

30. The chimeric influenza virus HA polypeptide of claim 1 , wherein the HA globular head domain is from an influenza virus of subtype H13.

31. The chimeric influenza virus HA polypeptide of claim 1 , wherein the HA globular head domain is from an influenza virus of subtype H14.

32. The chimeric influenza virus HA polypeptide of claim 1 , wherein the HA globular head domain is from an influenza virus of subtype H15.

33. The chimeric influenza virus HA polypeptide of claim 1 , wherein the HA globular head domain is from an influenza virus of subtype H16.

34. The chimeric influenza virus HA polypeptide of claim 27 , wherein the HA globular head domain is from an influenza virus of subtype H17.

35. The chimeric influenza virus HA polypeptide of claim 1 , wherein the HA stem domain is from an H1 subtype and the HA globular head domain from an H2 subtype.

36. The chimeric influenza virus HA polypeptide of claim 1 , wherein the HA stem domain is from an H1 subtype and the HA globular head domain from an H3 subtype.

37. The chimeric influenza virus HA polypeptide of claim 1 , wherein the HA stem domain is from an H1 subtype and the HA globular head domain from an H11 subtype.

38. The chimeric influenza virus HA polypeptide of claim 14 , wherein the HA stem domain is from an influenza virus of subtype H1.

39. The chimeric influenza virus HA polypeptide of claim 14 , wherein the HA stem domain is from an influenza virus of subtype H3.

40. The chimeric influenza virus HA polypeptide of claim 14 , wherein the HA globular head domain is the HA globular head domain of an influenza virus of subtype H4, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, or H17.

41. The chimeric influenza virus HA polypeptide of claim 14 , wherein the HA globular head domain is from an influenza virus of subtype H5.

42. The chimeric influenza virus HA polypeptide of claim 14 , wherein the HA stem domain is from A/Perth/16/2009 of the H3 subtype and the HA globular head domain is from A/mallard/Alberta/24/2001 of the H7 subtype.

43. The chimeric influenza virus HA polypeptide of claim 38 , wherein the H1 subtype is A/California/04/09.

44. The chimeric influenza virus HA polypeptide of claim 39 , wherein the H3 subtype is A/Perth/16/2009.

45. The chimeric influenza viais HA polypeptide of claim 14 , wherein the HA stem domain is from an H3 subtype and the HA globular head domain from an H5 subtype.

46. The chimeric influenza virus HA polypeptide of claim 45 , wherein the H3 subtype is A/Perth/16/2009 and the H5 subtype is A/Vietnam/1203/04.

47. The chimeric influenza virus HA polypeptide of claim 1 , wherein (a) the HA stem domain is from A/PR/8/34 of the H1 subtype and the HA globular head domain is from A/California/04/09 of the H1 subtype; (b) the HA stem domain is from A/PR/8/34 of the H1 subtype and the HA globular head domain is from A/Vietnam/1203/04 of the H5 subtype; (c) the HA stem domain is from A/PR/8/34 of the H3 subtype and the HA globular head domain is from A/Hong Kong/1/1968 of the H3 subtype; (d) the HA stem domain is from A/PR/8/34 of the H1 subtype and the HA globular head domain is from A/Mallard/Sweden/81/02 of the H6 subtype; or (e) the HA stem domain is from A/PR/8/34 and the HA globular head domain is from A/Guinea fowl/Hong Kong/WF 10/99 of the H9 subtype.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 27, 2014
From: GARCIA-SASTRE, ADOLFO; PALESE, PETER; KRAMMER, FLORIAN; PICA, NATALIE; EGGINK, DIRK; MEDINA-SILVA, RAFAEL A.; HAI, RONG
To: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
Reel/Frame 032966/0258 →
CONFIRMATORY LICENSE Recorded Mar 27, 2014
From: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 032547/0261 →
Continuity (7)
Provisional Application 61684481 · Aug 17, 2012
Provisional Application 61670108 · Jul 10, 2012
Provisional Application 61648525 · May 17, 2012
Provisional Application 61607526 · Mar 6, 2012
Provisional Application 61565899 · Dec 1, 2011
Provisional Application 61536924 · Sep 20, 2011
Related Publication 20150132330A1 · May 14, 2015
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