IP Library › Granted Patent US 10,137,189

Granted Patent B2

US 10,137,189 · App. 15/158,785 · Granted Nov 27, 2018

Influenza virus vaccines and uses thereof

Inventors: Adolfo Garcia-Sastre (New York, NY); Peter Palese (New York, NY); Florian Krammer (New York, NY)

Assignee: Icahn School of Medicine at Mount Sinai

A61K39/145 A61K39/12 C07K14/005 C12N7/00 A61K2039/521 A61K2039/5252 A61K2039/54 A61K2039/543 A61K2039/545 A61K2039/55 A61K2039/70 C12N2760/16123 C12N2760/16134 C12N2760/16223 C12N2760/16234

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Quick Facts

Patent No.: US 10,137,189
App. No.: 15/158,785
Granted: Nov 27, 2018
Kind: B2

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Abstract

Provided herein are chimeric influenza hemagglutinin (HA) polypeptides, compositions comprising the same, vaccines comprising the same, and methods of their use.

Claims (76)

1. A method of immunizing a subject against an influenza virus comprising:

(a) administering to the subject an effective amount of a first immunogenic composition comprising a first chimeric hemagglutinin (HA) polypeptide, wherein the first chimeric HA polypeptide comprises an influenza virus hemagglutinin stem domain and an influenza virus hemagglutinin globular head domain, wherein the influenza virus hemagglutinin globular head domain is heterologous to the influenza virus hemagglutinin stem domain; and

(b) subsequent to the administration of the first immunogenic composition to the subject, administering to the subject an effective amount of a second immunogenic composition comprising a second chimeric hemagglutinin (HA) polypeptide, wherein the second chimeric HA polypeptide comprises the stem domain of the HA from influenza virus A/California/4/2009 (H1N1) and the globular head domain of the HA from an influenza virus A/Vietnam/1203/2004 (H5), A/Indonesia/5/2005 (H5), A/Anhui/1/2005 (H5), A/Bar headed loose/Quinghai/1A/2005(H5), A/turkey/Turkey/1/2005 (H5), or A/whooperswan/Mongolia/244/2005 (H5),

and wherein the globular head domain of the first chimeric influenza virus HA polypeptide is different than the globular head domain of the second chimeric HA polypeptide.

2. A method of immunizing a subject against an influenza virus comprising:

(b) subsequent to the administration of the first immunogenic composition to the subject, administering to the subject an effective amount of a second immunogenic composition comprising a second chimeric hemagglutinin (HA) polypeptide, wherein the second chimeric HA polypeptide comprises the stem domain of the HA from influenza virus A/Perth/16/2009 (H3N2) and the globular head domain of the HA from an influenza virus A/Netherlands/219/03 (H7), A/Canada/504/04 (H7), A/Canada/444/04 (H7), A/chicken/Jalisco/CPA1/2012 (H7), A/mallard/Alberta/24/2001 (H7), A/rhea/NC/39482/93 (H7), or A/mallard/Netherlands/12/2000 (H7),

and wherein the globular head domain of the first chimeric HA polypeptide is different than the globular head domain of the second chimeric HA polypeptide.

3. The method of claim 1 , wherein the first chimeric HA polypeptide comprises the stem domain of the HA from influenza virus A/Perth/16/2009 (H3N2) and the globular head domain of the HA from an influenza virus A/Netherlands/219/03 (H7), A/Canada/504/04 (H7), A/Canada/444/04 (H7), A/chicken/Jalisco/CPA1/2012 (H7), A/mallard/Alberta/24/2001 (H7), A/rhea/NC/39482/93 (H7), or A/mallard/Netherlands/12/2000 (H7) .

4. The method of claim 2 , wherein the first chimeric HA polypeptide comprises the stem domain of the HA from influenza virus A/California/4/2009 (H1N1) and the globular head domain of the HA from an influenza virus A/Vietnam/1203/2004 (H5), A/Indonesia/5/2005 (H5), A/Anhui/1/2005 (H5), A/Bar headed goose/Quinghai/1A/2005(H5), A/turkey/Turkey/1/2005 (H5), or A/whooperswan/Mongolia/244/2005 (H5) .

5. A method of immunizing a subject against an influenza virus comprising administering to the subject an effective amount of an immunogenic composition comprising a first chimeric HA polypeptide and a second chimeric HA polypeptide, wherein the first chimeric HA polypeptide comprises the stem domain of the HA from influenza virus A/Perth/16/2009 (H3 N2) and the globular head domain of the HA from an influenza virus A/Netherlands/219/03 (H7), A/Canada/504/04 (H7), A/Canada/444/04 (H7), A/chicken/Jalisco/CPA1/2012 (H7), A/mallard/Alberta/24/2001 (H7) , A/rhea/NC/39482/93 (H7) , or A/mallard/Netherlands/12/2000 (H7), and wherein the second chimeric HA polypeptide comprises the stem domain of the HA from influenza virus A/California/4/2009 (H1N1) and the globular head domain of the HA from an influenza virus A/Vietnam/1203/2004 (H5), A/Indonesia/5/2005 (H5), A/Anhui/1/2005 (H5), A/Bar headed goose/Quinghai/1A/2005 (H5), A/turkey/Turkey/1/2005 (H5), or A/whooperswan/Mongolia/244/2005 (H5).

6. The method of claim 1 , wherein the first immunogenic composition and/or the second immunogenic composition is a multivalent vaccine.

7. The method of claim 2 , wherein the first immunogenic composition and/or second immunogenic composition is a multivalent vaccine.

8. A method of immunizing a subject against an influenza virus comprising:

(a) administering to the subject an effective amount of a first immunogenic composition comprising a first inactivated virus or live attenuated virus, wherein the first inactivated virus or live attenuated virus contains a first chimeric HA polypeptide, wherein the first chimeric HA polypeptide comprises an influenza virus hemagglutinin stem domain and an influenza virus hemagglutinin globular head domain, wherein the influenza virus hemagglutinin globular head domain is heterologous to the influenza virus hemagglutinin stem domain; and

(b) subsequent to the administration of the first immunogenic composition, administering to the subject an effective amount of a second immunogenic composition comprising a second inactivated virus or live attenuated virus, wherein the second inactivated virus or live attenuated virus contains a second chimeric HA polypeptide, wherein the second chimeric HA polypeptide comprises the stem domain of the HA from influenza virus A/Perth/16/2009 (H3N2) and the globular head domain of the HA from an influenza virus A/Netherlands/219/03 (H7), A/Canada/504/04 (H7), A/Canada/444/04 (H7), A/chicken/Jalisco/CPA1/2012 (H7), A/mallard/Alberta/24/2001 (H7), A/rhea/NC/39482/93 (H7), or A/mallard/Netherlands/12/2000 (H7),

and wherein the globular head domain of the first chimeric influenza virus HA polypeptide is different than the globular head domain of the second chimeric HA polypeptide.

9. A method of immunizing a subject against an influenza virus comprising:

(b) subsequent to the administration of the first immunogenic composition, administering to the subject an effective amount of a second immunogenic composition comprising a second inactivated virus or live attenuated virus, wherein the second inactivated virus or live attenuated virus contains a second chimeric HA polypeptide, wherein the second chimeric HA polypeptide comprises the stem domain of the HA from influenza virus A/California/4/2009 (H1N1) and the globular head domain of the HA from an influenza virus A/Vietnam/1203/2004 (H5), A/Indonesia/5/2005 (H5), A/Anhui/1/2005 (H5), A/Bar headed goose/Quinghai/1A/2005 (H5), A/turkey/Turkey/1/2005 (H5), or A/whooperswan/Mongolia/244/2005 (H5),

and wherein the globular head domain of the first chimeric influenza virus HA polypeptide is different than the globular head domain of the second chimeric HA polypeptide.

10. The method of claim 8 , wherein the first chimeric HA polypeptide comprises the stem domain of the HA from influenza virus A/California/4/2009 (H1N1) and the globular head domain of the HA from an influenza virus A/Vietnam/1203/2004 (H5), A/Indonesia/5/2005 (H5), A/Anhui/1/2005 (H5), A/Bar headed goose/Quinghai/1A/2005 (H5), A/turkey/Turkey/1/2005 (H5), or A/whooperswan/Mongolia/244/2005 (H5).

11. The method of claim 9 , wherein the first chimeric HA polypeptide comprises the stem domain of the HA from influenza virus A/Perth/16/2009 (H3N2) and the globular head domain of the HA from an influenza virus A/Netherlands/219/03 (H7), A/Canada/504/04 (H7), A/Canada/444/04 (H7), A/chicken/Jalisco/CPA1/2012 (H7), A/mallard/Alberta/24/2001 (H7), A/rhea/NC/39482/93 (H7), or A/mallard/Netherlands/12/2000 (H7).

12. A method of immunizing a subject against an influenza virus comprising administering to the subject an effective amount of an immunogenic composition comprising (i) a first inactivated virus or live attenuated virus, and (ii) a second inactivated virus or live attenuated virus, wherein the first inactivated virus or live attenuated virus contains a first chimeric HA polypeptide, wherein the first chimeric HA polypeptide comprises the stem domain of the HA from influenza virus A/Perth/16/2009 (H3N2) and the globular head domain of the HA from an influenza virus A/Netherlands/219/03 (H7), A/Canada/504/04 (H7), A/Canada/444/04 (H7), A/chicken/Jalisco/CPA1/2012 (H7), A/mallard/Alberta/24/2001 (H7), A/rhea/NC/39482/93 (H7), or A/mallard/Netherlands/12/2000 (H7), and wherein the second inactivated virus or live attenuated virus contains a second chimeric HA polypeptide, wherein the second chimeric HA polypeptide comprises the stem domain of the HA from influenza virus A/California/4/2009 (H1N1) and the globular head domain of the HA from an influenza virus A/Vietnam/1203/2004 (H5 ), A/Indonesia/5/2005 (H5), A/Anhui/1/2005 (H 5), A/Bar headed goose/Quinghai/1A/2005 (H5), A/turkey/Turkey/1/2005 (H 5), or A/whooperswan/Mongolia/244/2005 (H5).

13. The method of claim 8 , wherein the first immunogenic composition and/or the second immunogenic composition is a multivalent vaccine.

14. The method of claim 9 , wherein the first immunogenic composition and/or the second immunogenic composition is a multivalent vaccine.

15. The method of claim 1 , wherein

(i) the HA stem domain of the first chimeric HA polypeptide comprises (1) an HA1 N-terminal stem segment, wherein the HA1 N-terminal stem segment consists of amino acid residues HA1 N-term through A p ; (2) an HA1C-terminal stem segment, wherein the HA1 C-terminal stem segment consists of amino acid residues A q through HA1 C-term; and (3) an HA2domain;

(ii) the HA globular head domain of the first chimeric HA polypeptide comprises the amino acid residues between A p and A q of an HA1 domain;

(iii) the HA stem domain of the second chimeric HA polypeptide comprises (1) an HA1 N-terminal stem segment, wherein the HA1 N-terminal stem segment consists of amino acid residues HA1 N-term through A p ; (2) an HA 1 C-terminal stem segment, wherein the HA1 C-terminal stem segment consists of amino acid residues A q through HA1 C-term; and (3) an HA2 domain; and

(iv) the HA globular head domain of the second chimeric HA polypeptide comprises the amino acid residues between A p and A q of an HA1 domain;

wherein HA1 N-term is the N-terminal amino acid of a mature HA0 protein lacking a signal peptide; wherein HA1 c-term is the C-terminal amino acid of an HA1 domain; and wherein A p is the Cys that corresponds to amino acid position 52 of an HA1domain using H3 numbering; and wherein A q is the Cys that corresponds to amino acid position 277 of an HA1 domain using H3numbering.

16. The method of claim 2 , wherein

the HA stem domain of the first chimeric HA polypeptide comprises (1) an HA1 N-terminal stem segment, wherein the HA1 N-terminal stem segment consists of amino acid residues HA1 N-term through A p ; (2) an HA1 C-terminal stem segment, wherein the HA1 C-terminal stem segment consists of amino acid residues A q through HA1 C-term; and (3) an HA2domain;

(ii) the HA globular head domain of the first chimeric HA polypeptide comprises the amino acid residues between A p and A q of an HA1 domain;

(iii) the HA stem domain of the second chimeric HA polypeptide comprises (1) an HA1 N-terminal stem segment, wherein the HA1 N-terminal stem segment consists of amino acid residues HA1 N-term through A p ; (2) an HA1C-terminal stem segment, wherein the HA1C-terminal stem segment consists of amino acid residues A q through HA1 c-term ; and (3) an HA2 domain; and

(iv) the HA globular head domain of the second chimeric HA polypeptide comprises the amino acid residues between A p and A q of an HA1 domain;

wherein HA1 N-term is the N-terminal amino acid of a mature HA0 protein lacking a signal peptide; wherein HA1 c-term is the C-terminal amino acid of an HA1 domain; and wherein A p is the Cys that corresponds to amino acid position 52 of an HA1 domain using H3 numbering; and wherein A q is the Cys that corresponds to amino acid position 277 of an HA1 domain using H3numbering.

17. The method of claim 5 , wherein

(i)the HA stem domain of the first chimeric HA polypeptide comprises (1) an HA1 N-terminal stem segment, wherein the HA1 N-terminal stem segment consists of amino acid residues HA1 N-term through A p ; (2) an HA1 C-terminal stem segment, wherein the HA1 C-terminal stem segment consists of amino acid residues A q through HA1 C-term; and (3) an HA2domain;

(ii) the HA globular head domain of the first chimeric HA polypeptide comprises the amino acid residues between A p and A q of an HA1 domain;

(iii) the HA stem domain of the second chimeric HA polypeptide comprises (1) an HA1 N-terminal stem segment, wherein the HA1 N-terminal stem segment consists of amino acid residues HA1 N-term through A p ; (2) an HA1 C-terminal stem segment, wherein the HA1 C-terminal stem segment consists of amino acid residues A q through HA1 c-term ; and (3) an HA2 domain; and

(iv) the HA globular head domain of the second chimeric HA polypeptide comprises the amino acid residues between A p and A q of an HA1 domain;

wherein A q is the Cys that corresponds to amino acid position 277 of an HA1 domain using H3 numbering.

18. The method of claim 8 , wherein

(i)the HA stem domain of the first chimeric HA polypeptide comprises (1) an HA1 N-terminal stem segment, wherein the HA1 N-terminal stem segment consists of amino acid residues HA1 N-term through A p ; (2) an HA1 C-terminal stem segment, wherein the HA1 C-terminal stem segment consists of amino acid residues A q through HA1 C-term; and (3) an HA2 domain;

(ii) the HA globular head domain of the first chimeric HA polypeptide comprises the amino acid residues between A p and A q of an HA1 domain;

(iii) the HA stem domain of the second chimeric HA polypeptide comprises ( 1 ) an HA1 N-terminal stem segment, wherein the HA1 N-terminal stem segment consists of amino acid residues HA1 N-term through A p ; (2) an HA1 C-terminal stem segment, wherein the HA1 C-terminal stem segment consists of amino acid residues A q through HA1 c-term ; and (3) an HA2domain; and

(iv) the HA globular head domain of the second chimeric HA polypeptide comprises the amino acid residues between A p and A q of an HA1 domain;

wherein HA1 N-term is the N-terminal amino acid of a mature HA0 protein lacking a signal peptide; wherein HA1 C-term is the C-terminal amino acid of an HA1 domain; and wherein A p is the Cys that corresponds to amino acid position 52 of an HA1 domain using H3numbering; and wherein A q is the Cys that corresponds to amino acid position 277 of an HA1 domain using H3numbering.

19. The method of claim 9 , wherein

(i) the HA stem domain of the first chimeric HA polypeptide comprises (1) an HA1 N-terminal stem segment, wherein the HA1 N-terminal stem segment consists of amino acid residues HA1 N-term through A p ; (2) an HA1 C-terminal stem segment, wherein the HA1 C-terminal stem segment consists of amino acid residues A q through HA1 C-term; and (3) an HA2domain;

(ii) the HA globular head domain of the first chimeric HA polypeptide comprises the amino acid residues between A p and A q of an HA1 domain;

(iii) the HA stem domain of the second chimeric HA polypeptide comprises (1) an HA1 N-terminal stem segment, wherein the HA1 N-terminal stem segment consists of amino acid residues HA1 N-term through A p ; (2) an HA1 C-terminal stem segment, wherein the HA1 C-terminal stem segment consists of amino acid residues A q through HA1 c-term ; and (3) an HA2 domain; and

(iv) the HA globular head domain of the second chimeric HA polypeptide comprises the amino acid residues between A p and A q of an HA1 domain;

wherein HA1 N-term is the N-terminal amino acid of a mature HA0 protein lacking a signal peptide; wherein HA1 c-term is the C-terminal amino acid of an HA1 domain; and wherein A p is the Cys that corresponds to amino acid position 52 of an HA1 domain using H3 numbering; and wherein A q is the Cys that corresponds to amino acid position 277 of an HA1 domain using H3numbering.

20. The method of claim 12 , wherein

(ii) the HA globular head domain of the first chimeric HA polypeptide comprises the amino acid residues between A p and A q of an HA1 domain;

(iii) the HA stem domain of the second chimeric HA polypeptide comprises (1) an HA1 N-terminal stem segment, wherein the HA1 N-terminal stem segment consists of amino acid residues HA1 N-term through A p ; (2) an HA1 C-terminal stem segment, wherein the HA1 C-terminal stem segment consists of amino acid residues A q through HA1 c-term ; and (3) an HA2domain; and

(iv) the HA globular head domain of the second chimeric HA polypeptide comprises the amino acid residues between A p and A q of an HA1 domain;

wherein HA1 N-term is the N-terminal amino acid of a mature HA0 protein lacking a signal peptide; wherein HA1 c-term is the C-terminal amino acid of an HA1 domain; and wherein A p is the Cys that corresponds to amino acid position 52 of an HA1 domain using H3 numbering; and wherein A q is the Cys that corresponds to amino acid position 277 of an HA1 domain using H3numbering.

21. The method of claim 8 , wherein the immunogenic composition comprises (i) a first inactivated virus, and (ii) a second inactivated virus, wherein the first inactivated virus is a first split virus, and wherein the second inactivated virus is a second split virus.

22. The method of claim 19 , wherein the immunogenic composition comprises (i) a first inactivated virus, and (ii) a second inactivated virus, wherein the first inactivated virus is a first split virus, and wherein the second inactivated virus is a second split virus.

23. The method of claim 20 , wherein the immunogenic composition comprises (i) a first inactivated virus, and (ii) a second inactivated virus, wherein the first inactivated virus is a first split virus, and wherein the second inactivated virus is a second split virus.

24. The method of claim 21 , wherein the immunogenic composition comprises an adjuvant.

25. The method of claim 22 , wherein the immunogenic composition comprises an adjuvant.

26. The method of claim 23 , wherein the immunogenic composition comprises an adjuvant.

27. The method of claim 1 , wherein the second chimeric HA polypeptide comprises the stem domain of the HA from influenza virus A/California/4/2009 (H1N1) and the globular head domain of the HA from influenza virus A/Vietnam/1203/04 (H5 ).

28. The method of claim 2 , wherein the first chimeric HA polypeptide comprises the stem domain of the HA from influenza virus A/California/4/2009 (H1N1) and the globular head domain of the HA from influenza virus A/Vietnam/1203/04 (H5).

29. The method of claim 5 , wherein the second chimeric HA polypeptide comprises the stem domain of the HA from influenza virus A/California/4/2009 (H1N1) and the globular head domain of the HA from influenza virus A/Vietnam/1203/04 (H5 ).

30. The method of claim 8 , wherein the first chimeric HA polypeptide comprises the stem domain of the HA from influenza virus A/California/4/2009 (H1N1) and the globular head domain of the HA from influenza virus A/Vietnam/1203/04 (H5).

31. The method of claim 9 , wherein the second chimeric HA polypeptide comprises the stem domain of the HA from influenza virus A/California/4/2009 (H1N1) and the globular head domain of the HA from influenza virus A/Vietnam/1203/04 (H5).

32. The method of claim 12 , wherein the second chimeric HA polypeptide comprises the stem domain of the HA from influenza virus A/California/4/2009 (H1N1) and the globular head domain of the HA from influenza virus A/Vietnam/1203/04 (H5).

33. The method of claim 23 , wherein the second chimeric HA polypeptide comprises the stem domain of the HA from influenza virus A/California/4/2009 (H1N1) and the globular head domain of the HA from influenza virus A/Vietnam/1203/04 (H5).

Assignments (1)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 24, 2018

From: GARCIA-SASTRE, ADOLFO; PALESE, PETER; KRAMMER, FLORIAN

To: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI

Reel/Frame 046436/0648 →

Continuity (4)

Division 14109358 · Dec 17, 2013

Provisional Application 61738672 · Dec 18, 2012

Provisional Application 61840899 · Jun 28, 2013

Related Publication 20160361408A1 · Dec 15, 2016

Cited By (4)

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