Broadly reactive viral antigens as immunogens, compositions and methods of use thereof
Provided herein are non-naturally occurring, broadly reactive antigens derived from influenza viruses or avian infectious bronchitis virus (IBV) that are immunogenic and capable of eliciting a broadly reactive immune response, e.g., a broadly reactive neutralizing antibody response, directed against influenza virus antigens or IBV antigens following introduction into a subject. Also provided are non-naturally, broadly reactive immunogens, vaccines, virus-like particles (VLPs) and compositions comprising the immunogens and vaccines. Methods of generating an immune response in a human or non-human subject by administering the immunogens, vaccines, VLPs, or compositions thereof are provided. In particular, the immunogens comprise broadly reactive hemagglutinin (HA) protein antigens of influenza virus strains, such as H1, H2, H3, H5, or H7, or of IBV. The immunogens also comprise broadly reactive viral neuraminidase (NA) protein antigens.
1 . A non-naturally occurring and immunogenic influenza virus antigen, which comprises or consists of the amino acid sequence of a hemagglutinin (HA) antigen as set forth in SEQ ID NO: 1.
2 . The influenza virus antigen of claim 1 , wherein the influenza virus is an H1 influenza virus.
3 . A non-naturally occurring and immunogenic influenza virus antigen, which comprises or consists of the amino acid sequence of a neuraminidase (NA) antigen as set forth in SEQ ID NO: 8.
4 . The influenza virus antigen of claim 3 , wherein the NA antigen is an N2 NA-A antigen.
5 . A virus-like particle (VLP) comprising the influenza virus HA antigen of claim 1 .
6 . The VLP of claim 5 , which comprises a polynucleotide encoding the influenza virus HA antigen.
7 . A non-naturally occurring immunogen capable of generating an immune response against present and future influenza virus strains; wherein the immunogen comprises or consists of the amino acid sequence of a hemagglutinin (HA) antigen as set forth in SEQ ID NO: 1, and/or wherein the immunogen comprises or consists of the amino acid sequence of a neuraminidase (NA) antigen as set forth in SEQ ID NO: 8.
8 . The immunogen of claim 7 , wherein the immune response comprises the production of neutralizing antibodies and/or the production of T lymphocytes.
9 . The immunogen of claim 7 , wherein the immune response comprises the production of antibodies having hemagglutinin inhibitory activity and/or neuraminidase inhibitory activity.
10 . A pharmaceutically acceptable composition comprising the virus antigen of claim 1 and a pharmaceutically acceptable carrier, diluent, or excipient.
11 . An immunogenic composition or vaccine comprising the virus antigen of claim 1 .
12 . A pharmaceutically acceptable composition comprising the immunogenic composition or vaccine of claim 11 and a pharmaceutically acceptable carrier, diluent, or excipient.
13 . A method of generating an immune response in a subject, the method comprising administering to the subject an effective amount of the pharmaceutically acceptable composition of claim 12 .
14 . The method of claim 13 , wherein the subject is a human subject.
15 . An isolated polynucleotide encoding the virus antigen of claim 1 .
16 . A composition comprising the isolated polynucleotide of claim 15 and a pharmaceutically acceptable carrier, diluent, or excipient.
17 . A virus-like particle (VLP) comprising the polynucleotide of claim 15 .
18 . The immunogen of claim 7 , wherein the immune response comprises the production of antibodies having neuraminidase inhibitory activity.
19 . A pharmaceutically acceptable composition comprising the VLP of claim 5 and a pharmaceutically acceptable carrier, diluent, or excipient.
20 . A pharmaceutically acceptable composition comprising the immunogen of claim 7 and a pharmaceutically acceptable carrier, diluent, or excipient.
21 . The influenza virus antigen of claim 1 , which is a recombinant or synthetic antigen.
22 . The immunogen of claim 7 , which is recombinant or synthetic.
23 . A virus-like particle (VLP) comprising the influenza virus NA antigen of claim 3 .
24 . The VLP of claim 23 , which comprises a polynucleotide encoding the influenza virus NA antigen.
25 . A pharmaceutically acceptable composition comprising the virus antigen of claim 3 and a pharmaceutically acceptable carrier, diluent, or excipient.
26 . An immunogenic composition or vaccine comprising the virus antigen of claim 3 .
27 . A pharmaceutically acceptable composition comprising the immunogenic composition or vaccine of claim 26 and a pharmaceutically acceptable carrier, diluent, or excipient.
28 . An isolated polynucleotide encoding the virus antigen of claim 3 .
29 . A composition comprising the isolated polynucleotide of claim 28 and a pharmaceutically acceptable carrier, diluent, or excipient.
30 . A virus-like particle (VLP) comprising the polynucleotide of claim 28 .
31 . A pharmaceutically acceptable composition comprising the VLP of claim 30 and a pharmaceutically acceptable carrier, diluent, or excipient.
32 . The influenza virus antigen of claim 3 , which is a recombinant or synthetic antigen.
33 . A method of generating an immune response in a subject, the method comprising administering to the subject an effective amount of the pharmaceutically acceptable composition of claim 25 .
34 . The method of claim 33 , wherein the subject is a human subject.