Chimeric influenza vaccines

Patent metadata

Field	Value
Publication number	US-11992525-B2
Application number	US-202318501578-A
Country	US
Kind code	B2
Filing date	Nov 3, 2023
Priority date	May 8, 2020
Publication date	May 28, 2024
Grant date	May 28, 2024

Abstract

The present disclosure relates to a chimeric influenza virus hemagglutinin (HA) polypeptide, comprising one or more stem domain sequence, each having at least 60% homology with a stem domain consensus sequence of H1 subtype HA (H1 HA) and/or H5 subtype HA (H5 HA), fused with one or more globular head domain sequence, each having at least 60% homology with a globular head domain consensus sequence of H1 subtype HA (H1 HA) or H5 subtype HA (H5 HA).

First claim

What is claimed is:

1. An immunogenic composition comprising a monoglycosylated chimeric influenza virus hemagglutinin (HA) polypeptide and an adjuvant;
wherein the monoglycosylated chimeric influenza virus HA polypeptide comprising an amino acid sequence of SEQ ID NO: 4;
wherein the monoglycosylated chimeric influenza virus HA polypeptide has only N-Acetylglucosamine (GlcNAc) at N28, N40, N182, N292, and N497; and
wherein the adjuvant is selected from the group consisting of Al(OH) 3 , AlPO 4 , an analog of α-galactosylceramide (α-GalCer), squalene and QS21.

2. The immunogenic composition of claim 1 , wherein the monoglycosylated chimeric influenza virus HA polypeptide further comprises only N-Acetylglucosamine (GlcNAc) at N171 and N303.

3. The immunogenic composition of claim 1 , wherein the adjuvant is Al(OH) 3 .

4. The immunogenic composition of claim 1 , wherein the analog of a-galactosylceramide is C34.

5. The immunogenic composition of claim 1 , wherein the monoglycosylated chimeric influenza virus HA polypeptide is existed as a trimer.

6. A method of immunizing a subject against influenza virus or preventing an influenza virus disease comprising administering an effective amount of the immunogenic composition of claim 1 to the subject.

7. The method of claim 6 , wherein the method elicits CD4 + and CD8 + T-cell immune responses.

8. The method of claim 6 , wherein the method induces stem-specific antibodies, with higher antibody-dependent cellular cytotoxicity (ADCC), better neutralizing and stronger cross-protection activities against H1, H3, H5 and H7 strains and subtypes.

9. The method of claim 6 , wherein the method enhances the vaccine efficacy with more IFN-γ, IL-4 and CD8+ memory T cells produced.

10. A method for preparing a chimeric influenza virus hemagglutinin (HA) polypeptide Swap H1/5, having one or more stem domain sequence fused with one or more globular head domain sequence, comprising: composing H1 as HA1 (amino acids 1-327 of SEQ ID NO: 8) And H5 as HA2 (amino acids 328503 of SEQ ID NO: 8) giving H1 as globular head and [H1+H5 (HA2)] as stem.

11. The method for preparing the chimeric influenza virus hemagglutinin (HA) polypeptide Swap H1/5 of claim 10 , wherein one or more glycosites on the chimeric influenza virus hemagglutinin (HA) polypeptide Swap H1/5 are monoglycosylated.

12. The method for preparing the chimeric influenza virus hemagglutinin (HA) polypeptide Swap H1/5 of claim 11 , wherein the monoglycosylated HA polypeptide Swap H1/5 has only N-Acetylglucosamine (GlcNAc) on each glycosite.

13. The method for preparing the chimeric influenza virus hemagglutinin (HA) polypeptide Swap H1/5 of claim 10 , wherein the chimeric influenza virus HA polypeptide Swap H1/5 comprises the amino acid sequence of SEQ ID NO: 8.

14. A method for preparing a chimeric influenza virus hemagglutinin (HA) polypeptide Swap H5/1, having one or more stem domain sequence fused with one or more globular head domain sequence, comprising: composing H5 as HA1 (amino acid 1-330 of SEQ ID NO: 12) And H1 as HA2 (amino acid 331-506 of SEQ ID NO: 12) giving H5 as globular head and [H5+H1 (HA2)] as stem.

15. The method for preparing the chimeric influenza virus hemagglutinin (HA) polypeptide Swap H5/1 of claim 14 , wherein one or more glycosites on the chimeric influenza virus hemagglutinin (HA) polypeptide Swap H5/1 are monoglycosylated.

16. The method for preparing the chimeric influenza virus hemagglutinin (HA) polypeptide Swap H5/1 of claim 15 , wherein the monoglycosylated HA polypeptide Swap H5/1 has only N-Acetylglucosamine (GlcNAc) on each glycosite.

17. The method for preparing the chimeric influenza virus hemagglutinin (HA) polypeptide Swap H5/1 of claim 14 , wherein the chimeric influenza virus HA polypeptide Swap H5/1 comprises the amino acid sequence of SEQ ID NO: 12.

18. A method for preparing a chimeric influenza virus hemagglutinin (HA) polypeptide chimeric H5/1, having one or more stem domain sequence fused with one or more globular head domain sequence, comprising:
(a) constructing the globular head domain with the amino acid sequence between residues C42 and C274 of SEQ ID NO: 4 (H3 numbering); and
(b) constructing the stem domain with portions of HA1 and HA2 subunits (amino acids 1˜41 of SEQ ID NO: 4 and 275-511 of SEQ ID NO: 4).

19. The method for preparing the chimeric influenza virus hemagglutinin (HA) polypeptide chimeric H5/1 of claim 18 , wherein one or more glycosites on the chimeric influenza virus hemagglutinin (HA) polypeptide chimeric H5/1 are monoglycosylated.

20. The method for preparing the chimeric influenza virus hemagglutinin (HA) polypeptide chimeric H5/1 of claim 19 , wherein the monoglycosylated HA polypeptide chimeric H5/1 has only N-Acetylglucosamine (GlcNAc) on each glycosite.

21. The method for preparing the chimeric influenza virus hemagglutinin (HA) polypeptide chimeric H5/1 of claim 18 , wherein the chimeric influenza virus HA polypeptide chimeric H5/1 comprises the amino acid sequence of SEQ ID NO: 4.

Assignees

• Academia Sinica

Inventors

• Wong Chi-Huey
• Liao Hsin-Yu
• Wang Shih-Chi
• Ko Yi-An
• Lin Kuo-I
• Ma Che
• Cheng Ting-Jen

Classifications

• A61K39/145 Primary

  Orthomyxoviridae, e.g. influenza virus · CPC title

• A61P31/16

  for influenza or rhinoviruses · CPC title

• C07K14/005

  from viruses · CPC title

• A61K2039/575

  humoral response · CPC title

• A61K39/12 Primary

  Viral antigens · CPC title