Nanoparticle-based influenza virus vaccines and uses thereof

Patent metadata

Field	Value
Publication number	US-12433943-B2
Application number	US-202017423565-A
Country	US
Kind code	B2
Filing date	Feb 7, 2020
Priority date	Feb 8, 2019
Publication date	Oct 7, 2025
Grant date	Oct 7, 2025

Abstract

Nanoparticles and vaccines containing these nanoparticles that elicit an immune response against hemagglutinin (HA) proteins from a broad range of influenza viruses are provided. The nanoparticles are made from self-assembling proteins, at least one of which is joined to an immunogenic portion of an influenza HA protein. This immunogenic portion is displayed on the nanoparticle surface, making the nanoparticles useful for vaccinating subjects against influenza virus.

First claim

What is claimed is:

1. A nanoparticle, comprising:
(a) a plurality of first assemblies, each first assembly comprising a plurality of identical first proteins; and,
(b) a plurality of second assemblies, each second assembly comprising a plurality of second proteins;
wherein at least one second assembly comprises at least one second protein joined to an immunogenic portion of an influenza hemagglutinin (HA) protein, thereby forming a fusion protein;
wherein the sequence of the first protein differs from the sequence of the second protein;
wherein the plurality of first assemblies non-covalently interact with the plurality of second assemblies to form the nanoparticle; and,

wherein the nanoparticle displays the immunogenic portion of an HA protein on its surface.

2. The nanoparticle of claim 1 , wherein each of the first proteins comprises an amino acid sequence at least 80%, 85%, 90%; 91%, 95%, 96%, 97%, 98%, or 99% identical, or 100% identical to a sequence selected from the group consisting of: SEQ ID NO:41, SEQ ID NO:43, SEQ ID NO:45, SEQ ID NO:47, SEQ ID NO:49, SEQ ID NO:51, SEQ ID NO:53, SEQ ID NO:55, SEQ ID NO:57, SEQ ID NO:59, SEQ ID NO:61, SEQ ID NO:32, SEQ ID NO:65, SEQ ID NO:67, SEQ ID NO:69, SEQ ID NO:71, SEQ ID NO:73, SEQ ID NO:75, SEQ ID NO:77, SEQ ID NO:79, SEQ ID NO:81, SEQ ID NO:83, SEQ ID NO:85, SEQ ID NO:87, SEQ ID NO:227, SEQ ID NO:229 SEQ ID NO:231 SEQ ID NO:233, SEQ ID NO:235, SEQ ID NO:237, SEQ ID NO:239, SEQ ID NO:241 SEQ ID NO:243, SEQ ID NO:267, SEQ ID NO:268, SEQ ID NO: 271, SEQ ID NO:273, SEQ ID NO:275, SEQ ID NO:282, SEQ ID NO:285, SEQ ID NO:287, SEQ ID NO:288, SEQ ID NO:291, SEQ ID NO:293, SEQ ID NO:295, SEQ ID NO:297, SEQ ID NO:299, SEQ ID NO:347, SEQ ID NO:348, and SEQ ID NO:349, and wherein a plurality of first proteins interact to form the first assemblies.

3. The nanoparticle of claim 1 , wherein each of the second protein comprises an amino acid sequence at least 80%, 85%, 90%, 91%, 95%, 96%, 97%, 98%, or 99% identical, or 100% identical to a sequence selected from the group consisting of SEQ ID NO:89, SEQ ID NO:245, SEQ ID NO:247, SEQ ID NO:249, SEQ ID NO:251, SEQ ID NO:253, SEQ ID NO:255, SEQ ID NO:257, SEQ ID NO:266, SEQ ID NO:269, SEQ ID NO:270, SEQ ID NO:272, SEQ ID NO:274, SEQ ID NO:283, SEQ ID NO:284, SEQ ID NO:286, SEQ ID NO:289, SEQ ID NO:290, SEQ ID NO:292, SEQ ID NO:294, SEQ ID NO:296, SEQ ID NO:298, and wherein a plurality of proteins non-covalently interact to form the second assemblies.

4. The nanoparticle of claim 1 , wherein the first protein and the second protein comprise amino acid sequences at least 80%, 85%, 90%, 91%, 95%, 96%, 97%, 98%, or 99% identical, or 100% identical, to the sequences of first and second proteins, respectively, selected from the pairs of first and second proteins in of SEQ ID NO:267 and SEQ ID NO:266; SEQ ID NO:268 and SEQ ID NO:269; SEQ ID NO:268 and SEQ ID NO:289; SEQ ID NO:288 and SEQ ID NO:269; SEQ ID NO:271 and SEQ ID NO:270; SEQ ID NO:291 and SEQ ID NO:270; SEQ ID NO:293 and SEQ ID NO:270; SEQ ID NO:271 and SEQ ID NO:290; SEQ ID NO:291 and SEQ ID NO:290; SEQ ID NO:293 and SEQ ID NO:290; SEQ ID NO:271 and SEQ ID NO:292; SEQ ID NO:291 and SEQ ID NO:292; SEQ ID NO:293 and SEQ ID NO:292; SEQ ID NO:273 and SEQ ID NO:272; SEQ ID NO:295 and SEQ ID NO:272; SEQ ID NO:297 and SEQ ID NO:272; SEQ ID NO:299 and SEQ ID NO:272; SEQ ID NO:273 and SEQ ID NO:294; SEQ ID NO:295 and SEQ ID NO:294; SEQ ID NO:297 and SEQ ID NO:294; SEQ ID NO:299 and SEQ ID NO:294; SEQ ID NO:273 and SEQ ID NO:296; SEQ ID NO:295 and SEQ ID NO:296; SEQ ID NO:297 and SEQ ID NO:296; SEQ ID NO:299 and SEQ ID NO:296; SEQ ID NO:273 and SEQ ID NO:298; SEQ ID NO:295 and SEQ ID NO:298; SEQ ID NO:297 and SEQ ID NO:298; SEQ ID NO:299 and SEQ ID NO:298; SEQ ID NO:275 and SEQ ID NO:274; SEQ ID NO:282 and SEQ ID NO:283; SEQ ID NO:285 and SEQ ID NO:284; SEQ ID NO:287 and SEQ ID NO:286; SEQ ID NO:288 and SEQ ID NO:289; SEQ ID NO:300 and SEQ ID NO:301; SEQ ID NO:303 and SEQ ID NO:302; SEQ ID NO:305 and SEQ ID NO:304; SEQ ID NO:306 and SEQ ID NO:307; SEQ ID NO:308 and SEQ ID NO:309; SEQ ID NO:310 and SEQ ID NO:311; SEQ ID NO:312 and SEQ ID NO:313; SEQ ID NO:314 and SEQ ID NO:315; SEQ ID NO:316 and SEQ ID NO:309; SEQ ID NO:317 and SEQ ID NO:318; SEQ ID NO:319 and SEQ ID NO:320; SEQ ID NO:321 and SEQ ID NO:322; SEQ ID NO:321 and SEQ ID NO:322; SEQ ID NO:307 and SEQ ID NO:306; SEQ ID NO:309 and SEQ ID NO:308; SEQ ID NO:311 and SEQ ID NO:310; SEQ ID NO:313 and SEQ ID NO:312; SEQ ID NO:315 and SEQ ID NO:314; SEQ ID NO:309 and SEQ ID NO:316; SEQ ID NO:318 and SEQ ID NO:317; SEQ ID NO:320 and SEQ ID NO:319; SEQ ID NO:322 and SEQ ID NO:321; or SEQ ID NO:89 and one of SEQ ID NO:41, 43, 45, 47, 49, 51, 53, 55, 57, 59, 61, 63, 65, 67, 69, 71, 73, 75, 77, 79, 81, 83, 85, 87, 347, 348, and 349.

5. The nanoparticle of claim 1 , wherein the second protein is joined to the immunogenic portion of an influenza HA protein by a linker.

6. The nanoparticle of claim 1 , wherein the immunogenic portion of the HA protein is derived from an HA protein from a Type A, Type B, or Type C influenza vims.

7. The nanoparticle of claim 1 , wherein the immunogenic portion of the HA protein is derived from an HA protein from an H1, H2, H3, H4, H5, H6, H7, H8, H9, H10, H11, H12, H13, H14, H15, H16, H17, or H18 influenza virus.

8. The nanoparticle of claim 1 , wherein the immunogenic portion of the HA protein comprises at least 6, 8, 10, 25, 50, 75, 100, 150, 200, 250, 300, 350, 400, 450, or 500, or more contiguous amino acid residues from a sequence at least 80%, 85%, 90%, 91%, 95%, 96%, 97%, 98%, or 99% identical, or 100% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 4, 7, 10, 13, 16, 19, 22, 25, 28, 31, 34, and 37.

9. The nanoparticle of claim 1 , wherein the immunogenic portion is from the head region of an influenza virus HA protein.

10. The nanoparticle of claim 1 , wherein the immunogenic portion comprises
(a) at least 6, 8, 10, 25, 50, 75, 100, or 200, or more contiguous amino acid residues from an amino acid sequence that corresponds to amino acid residues 59-291 of SEQ ID NO:1; or
(b) at least 6, 8, 10, 25, 50, 75, 100, or 200, or more contiguous amino acid residues from an amino acid sequence at least 80%, 85%, 90%, 91%, 95%, 96%, 97%, 98%, or 99% identical, or 100% identical to an amino acid sequence selected from the group consisting of SEQ ID NOs:2, 5, 8, 11, 14, 17, 20, 23, 26, 29, 32, 35, and 38.

11. The nanoparticle of claim 1 , wherein the immunogenic portion is from the stem region of an influenza virus HA protein.

12. The nanoparticle of claim 11 , wherein the immunogenic portion of an HA protein comprises
(a) at least 6, 8, 10, 25, or 50, or more contiguous amino acid residues, from a sequence that is at least 80%, 85%, 90%, 91%, 95%, 96%, 97%, 98%, or 99% identical, or 100% identical to amino acid residues 1-58 of SEQ ID NO: 1, amino acid residues 1-58 of SEQ ID NO:4, amino acid residues 1-67 of SEQ ID NO:7, amino acid residues 1-68 of SEQ ID NO:10, amino acid residues 1-68 of SEQ ID NO:13, amino acid residues 1-5 of SEQ ID NO:16, amino acid residues 1-57 of SEQ ID NO:19, amino acid residues 1-57 of SEQ ID NO:22, amino acid residues 1-59 of SEQ ID NO:25, amino acid residues 1-59 of SEQ ID NO:28, amino acid residues 1-58 of SEQ ID NO:31, amino acid residues 1-67 of SEQ ID NO:34, or amino acid residues 1-68 of SEQ ID NO:37; or
(b) at least 6, 8, 10, 25, 50, 75, 100, or 200, or more contiguous amino acid residues, from a sequence at least 80%, 85%, 90%, 91%, 95%, 96%, 97%, 98%, or 99% identical, or 100% identical to amino acid residues 292-517 of SEQ ID NO:1, amino acid residues 293-515 of SEQ ID NO:4, amino acid residues 294-517 of SEQ

Assignees

• The Usa As Represented By The Sec Dep Of Health And Human Services
• Unversity Of Washington
• Univ Washington

Inventors

• Kanekiyo Masaru
• Graham Barney S
• Boyoglu-Barnum Seyhan
• Gillespie Rebecca A
• King Neil P
• Ellis Daniel
• Wang Jing Yang
• Ueda george
• Fallas Jorge

Classifications

• C12N7/00

  Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof (preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00) · CPC title

• A61K2039/55555

  Liposomes; Vesicles, e.g. nanoparticles; Spheres, e.g. nanospheres; Polymers · CPC title

• A61P31/16

  for influenza or rhinoviruses · CPC title

• C12N2760/16234

  Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein · CPC title

• C12N2760/16134

  Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein · CPC title