Methods and compositions for vaccination against heterosubtypic influenza viruses using an adenoviral vector leading to enhanced t cell response through autophagy

Patent metadata

Field	Value
Publication number	US-2025152696-A1
Application number	US-202218683238-A
Country	US
Kind code	A1
Filing date	Aug 13, 2022
Priority date	Aug 13, 2021
Publication date	May 15, 2025
Grant date	—

Abstract

An adenoviral vector with E1 and E3 regions removed and expressing the nucleoprotein or other immunogenic domain(s) of an influenza virus with or without the presence of the Autophagy-Inducing Peptide C5 (AIP-C5) from the CFP10 protein of Mycobacterium tuberculosis , compositions comprising same, and methods of use for general vaccination against heterosubtypic influenza viruses.

First claim

We claim:

1 . An immunogenic composition comprising:
a full-length nucleoprotein (NP) of a H7N9 influenza virus with or without expressing 22 amino acid residues of Autophagy-Inducing Peptide C5 (AIP-C5) from a CFP10 protein of Mycobacterium tuberculosis , or a functional fragment thereof, and a pharmaceutically acceptable carrier; wherein the immunogenic composition is cross-protective against two or more subtypes of influenza viruses when administered to a subject.

2 . The immunogenic composition of claim 1 , wherein the composition is cross-protective against at least five subtypes of influenza viruses when administered to a subject.

3 . The immunogenic composition of claim 1 or 2 , wherein, when administered to a subject, the composition confers general immunogenicity protection against the subtypes of viruses selected from the group consisting of H1, H3, H5, H7, H9 and influenza B viruses.

4 . The immunogenic composition of claim 1 , wherein the composition is cross-protective against two or more subtypes of influenza A or B viruses when administered to a subject.

5 . The immunogenic composition of claim 1 , wherein the full-length NP or functional fragment thereof comprises SEQ ID NO: 1.

6 . The immunogenic composition of claim 1 or 5 , wherein the AIP-C5 from a CFP10 protein comprises SEQ ID NO: 3.

7 . The immunogenic composition of any one of claims 1, 2, 3, 4, 5, or 6 , further comprising an adjuvant.

8 . The immunogenic composition of any one of claims 1, 2, 3, 4, 5, or 6 formulated to be administered intranasally.

9 . The immunogenic composition of any one of claims 1, 2, 3, 4, 5, or 6 formulated to be administered subcutaneously.

10 . The immunogenic composition of any one of claims 1, 2, 3, 4, 5, or 6 formulated for oral administration.

11 . The immunogenic composition of any one of claims 1, 2, 3, 4, 5, or 6 formulated as an aerosol spray.

12 . An immunogenic composition comprising:
SEQ ID NO: 6, 8, 10, 12, or 14; and a pharmaceutically acceptable carrier; wherein the immunogenic composition is cross-protective against two or more subtypes of influenza viruses when administered to a subject.

13 . A human or bovine adenoviral (Ad) vector comprising a polynucleotide sequence that encodes a full-length nucleoprotein (NP) from H7N9 influenza virus, a functional fragment thereof and/or one or more other immunogenic domains of an influenza virus.

14 . The Ad vector of claim 13 , wherein the polynucleotide sequence further encodes Autophagy-Inducing Peptide C5 (AIP-C5) from the CFP10 protein of Mycobacterium tuberculosis.

15 . The Ad vector of claim 14 , wherein the AIP-C5 comprises 22 amino acid residues.

16 . The Ad vector of claim 13 , wherein the polynucleotide sequence comprises SEQ ID NO: 2.

17 . The Ad vector of any one of claim 12, 13, or 14 , wherein the polynucleotide sequence further comprises SEQ ID NO: 4.

18 . The Ad vector of claim 13 , wherein the full-length NP, functional fragment thereof and/or one or more other immunogenic domains of an influenza virus comprises SEQ ID NO: 1.

19 . The Ad vector of claim 13 , wherein the AIP-C5 comprises SEQ ID NO: 3.

20 . The Ad vector of claim 13 , wherein at least E1 and E3 regions are deleted.

21 . The Ad vector of claim 20 , wherein the polynucleotide sequence of the full-length NP, functional fragment thereof and/or one or more other immunogenic domains of an influenza virus is inserted in the deleted E1 region.

22 . The Ad vector of claim 19 , wherein at least E1 and E3 regions of the Ad are deleted and SEQ ID NO: 3 is inserted in the deleted E1 region of the Ad.

23 . The Ad vector of claim 13 , wherein said Ad provides protection against infection by various subtypes of viruses selected from the group consisting of H1, H3, H5, H7, H9, and influenza B viruses.

24 . The Ad vector of claim 13 , wherein the Ad is bovine Ad type 3 (BAd3).

25 . A human or bovine adenoviral (Ad) vector comprising a polynucleotide sequence comprising SEQ ID NO: 5, 7, 9, 11, 13, or 15, or a functional fragment thereof.

26 . A method of generating a general immunogenicity against a heterosubtypic influenza virus in a subject, comprising administering to said subject an effective amount of an immunogenic composition of any one of claims 1-13 or an adenoviral (Ad) vector of any one of claims 12-25 .

27 . The method of claim 26 , wherein said administration is intranasal.

28 . The method of claim 26 , wherein said administration is subcutaneous.

29 . The method of claim 26 , wherein said composition or Ad vector is administered orally.

30 . The method of claim 29 , wherein said composition or Ad vector is administered as an aerosol spray.

31 . The method of claim 26 , wherein said method provides a general immunogenicity protection to the subject against various subtypes of viruses selected from the group consisting of H1, H3, H5, H7, H9, and influenza B viruses.

32 . The method of claim 26 , wherein administration of the effective amount of the immunogenic composition or the Ad vector induces a dose-dependent increase in cell-mediated immunity in the subject.

33 . The method of claim 26 , wherein the subject is a human.

34 . The method of claim 26 , wherein said administration is intramuscular.

Assignees

• Purdue Research Foundation
• The Us Secretary Department Of Health And Human Service
• Methodist Hospital

Inventors

• Mittal Suresh
• Sambhara Suryaprakash
• Sayedahmed Ekramy
• Jagannath Chinnaswamy

Classifications

• A61K2039/70

  Multivalent vaccine · CPC title

• A61K2039/6068

  Other bacterial proteins, e.g. OMP · CPC title

• A61K2039/543

  intranasal · CPC title

• A61K2039/542

  oral/gastrointestinal · CPC title

• A61K2039/54

  characterised by the route of administration · CPC title