Mutant of hemagglutinin protein of H3N2 subtype influenza virus and use thereof

Patent metadata

Field	Value
Publication number	US-11426459-B2
Application number	US-201816756973-A
Country	US
Kind code	B2
Filing date	Oct 10, 2018
Priority date	Oct 18, 2017
Publication date	Aug 30, 2022
Grant date	Aug 30, 2022

Abstract

The disclosure relates to a mutant of hemagglutinin protein of H3N2 subtype influenza virus and use thereof. In addition, the disclosure also relates to a pharmaceutical composition (e.g., a vaccine) comprising the mutant, a method for preparing the mutant, and a method of using the mutant for prevention and/or treatment of an infection of influenza virus and/or a disease (e.g., an influenza) caused by the infection.

First claim

What is claimed is:

1. A mutant of hemagglutinin protein of H3N2 subtype influenza virus, wherein the mutant differs from a wild-type hemagglutinin protein of the H3N2 subtype influenza virus at least in that the N residue in each characteristic sequence N-X-(S or T) in the wild-type hemagglutinin protein is independently replaced with a non-N amino acid residue, so that the mutant contains no characteristic sequence N-X-(S or T); wherein, N represents asparagine, X represents any one amino acid other than proline, S represents serine, and T represents threonine; and optionally the mutant does not contain a N-terminal signal peptide and/or a transmembrane region of the wild-type hemagglutinin protein.

2. A recombinant protein, comprising the mutant according to claim 1 and an additional peptide segment, and the additional peptide segment is linked to the mutant.

3. A nucleic acid molecule, comprising or consisting of a nucleotide sequence encoding one of the following:
(i) the mutant according to claim 1 ; and
(ii) a recombinant protein comprising the mutant of (i) and an additional peptide segment linked to the mutant.

4. A vector, comprising the nucleic acid molecule according to claim 3 .

5. A host cell or virus, comprising
(i) the nucleic acid molecule according to claim 3 ; or
(ii) a vector comprising the nucleic acid molecule of (i).

6. A multimer, comprising or consisting of a plurality of
(i) the mutants according to claim 1 ; or
(ii) a recombinant protein comprising the mutant of (i) and an additional peptide segment linked to the mutant.

7. A pharmaceutical composition, comprising
a pharmaceutically acceptable carrier and/or excipient, and one or more of the following:
(i) the mutant according to claim 1 ;
(ii) a recombinant protein comprising the mutant of (i) and an additional peptide segment linked to the mutant; and
(iii) a multimer comprising or consisting of a plurality of the mutant of (i) or a plurality of the recombinant protein of (ii);
optionally, the pharmaceutical composition is a vaccine.

8. The mutant according to claim 1 , wherein the N residue in each characteristic sequence N-X-(S or T) in the wild-type hemagglutinin protein is independently conservatively replaced.

9. The mutant according to claim 1 , characterized by one or more of the following items:
(a) the wild-type hemagglutinin protein is from A/WISCONSIN/67/2005 (H3N2) or A/HONG_KONG/4801/2014 (H3N2);
(b) the wild-type hemagglutinin protein has a sequence selected from the group consisting of: SEQ ID NOs: 1 and 6;
(c) the wild-type hemagglutinin protein has an amino acid sequence as shown in SEQ ID NO: 1; and, optionally, the mutant does not contain amino acids 1-10 of SEQ ID NO: 1 and/or amino acids 504-550 of SEQ ID NO: 1;
(d) the wild-type hemagglutinin protein has an amino acid sequence as shown in SEQ ID NO: 6; and, optionally, the mutant does not contain amino acids 1-25 of SEQ ID NO: 6 and/or amino acids 518-565 of SEQ ID NO: 6; and
(e) the mutant has an amino acid sequence selected from the group consisting of SEQ ID NOs: 12-13; or, the mutant has an identity of at least 85%, at least 90%, at least 91%, and 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, at least 99% or 100% to an amino acid sequence selected from the group consisting of: SEQ ID NOs: 12-13; or, the mutant has an addition, deletion or substitution of one or more amino acid residues as compared to an amino acid sequence selected from the group consisting of: SEQ ID NOs: 12-13.

10. The recombinant protein according to claim 2 , characterized by one or more of the following items:
(a) the additional peptide segment is directly linked to the mutant or is linked to the mutant through a linker;
(b) the additional peptide segment is linked to the N-terminus or C-terminus of the mutant;
(c) the recombinant protein comprises at least 1, at least 2, at least 3, at least 5 or more additional peptide segments; and
(d) the additional peptide segment is selected from the group consisting of a signal peptide, a tag peptide, a folding motif, a detectable label, and any combination thereof.

11. The recombinant protein according to claim 10 , characterized by one or more of the following items:
(a) the signal peptide is linked to the N-terminus of the mutant;
(b) the signal peptide has an amino acid sequence as shown in SEQ ID NO: 9;
(c) the folding motif is linked to the C-terminus of the mutant; and
(d) the folding motif has an amino acid sequence as shown in SEQ ID NO: 10.

12. The host cell or virus according to claim 5 , wherein the virus is a baculovirus.

13. The multimer according to claim 6 , wherein the multimer is a trimer.

Assignees

• Univ Xiamen

Inventors

• Chen Yixin
• Shen Chenguang
• Chen Junyu
• Zhang Mengya
• Zhang Limin
• Xia Ningshao

Classifications

• C07K16/108

  Orthomyxoviridae (F), e.g. influenza virus · CPC title

• A61K2039/55505

  Inorganic adjuvants · CPC title

• C07K14/005 Primary

  from viruses · CPC title

• A61P31/16

  for influenza or rhinoviruses · CPC title

• C07K2319/00

  Fusion polypeptide · CPC title