Novel multivalent nanoparticle-based vaccines

Patent metadata

Field	Value
Publication number	US-2024226012-A1
Application number	US-202418615895-A
Country	US
Kind code	A1
Filing date	Mar 25, 2024
Priority date	Dec 31, 2014
Publication date	Jul 11, 2024
Grant date	—

Abstract

Novel, nanoparticle-based vaccines are provided that elicit an immune response to a broad range of infectious agents, such as influenza viruses. The nanoparticles comprise a heterogeneous population of fusion proteins, each comprising a monomeric subunit of a self-assembly protein, such as ferritin, joined to one or more immunogenic portions of a protein from an infectious agent, such as influenza virus. The fusion proteins self-assemble to form nanoparticles that display a heterogeneous population of immunogenic portions on their surface. When administered to an individual, such nanoparticles elicit an immune response to different strains, types, subtypes and species with in the same taxonomic family. Thus, such nanoparticles can be used to vaccinate an individual against infection by different Types, subtypes and/or strains of infectious agents. Also provided are specific fusion proteins, nucleic acid molecules encoding such fusion proteins and methods of using nanoparticles of the invention to vaccinate individuals.

First claim

What is claimed:

1 . A method of producing a nanoparticle, comprising:
culturing a cell comprising at least two nucleic acid molecules, wherein: each nucleic acid molecule encodes a unique species of self-assembling fusion protein, each fusion protein comprises a self-assembling, monomeric subunit protein joined to an immunogenic portion of an influenza virus hemagglutinin (HA) protein, wherein the immunogenic portion of the influenza virus HA protein is a receptor binding domain (RBD); the immunogenic portion in each species of self-assembling fusion protein differs from the immunogenic portion in the other species of self-assembling fusion proteins by at least one amino acid; the fusion proteins self-assemble to form a nanoparticle that displays on its surface, the immunogenic portions of the at least two species of self-assembling fusion proteins; at least one of the species of self-assembling fusion proteins comprises an amino acid sequence at least 80% identical to SEQ ID NO: 97; and the cell is cultured under conditions suitable for expressing the encoded self-assembling fusion proteins to form the nanoparticle.

2 . The method of claim 1 , wherein at least one of the species of self-assembling fusion proteins comprises an amino acid sequence at least 90% identical to SEQ ID NO: 97.

3 . The method of claim 1 , wherein at least one of the species of self-assembling fusion proteins comprises an amino acid sequence at least 95% identical to SEQ ID NO: 97.

4 . The method of claim 1 , wherein at least one of the species of self-assembling fusion proteins comprises an amino acid sequence at least 99% identical to SEQ ID NO: 97.

5 . The method of claim 1 , wherein the at least one species of self-assembling fusion protein comprises an amino acid sequence set forth as SEQ ID NO:97, SEQ ID NO:100, SEQ ID NO:103, SEQ ID NO: 106, SEQ ID NO:109, SEQ ID NO:112, SEQ ID NO:115, SEQ ID NO:118, SEQ ID NO:121, SEQ ID NO:124, SEQ ID NO:127, SEQ ID NO:130, SEQ ID NO:133, SEQ ID NO:136, SEQ ID NO:139, or SEQ ID NO:142.

6 . The method of claim 1 , wherein the at least one species of self-assembling fusion protein comprises an amino acid sequence set forth as SEQ ID NO: 97.

7 . A method of producing a nanoparticle, comprising:
culturing a cell comprising at least four nucleic acid molecules, wherein: each nucleic acid molecule encodes a unique species of self-assembling fusion protein, each fusion protein comprises a self-assembling, monomeric subunit protein joined to an immunogenic portion of an influenza virus hemagglutinin (HA) protein, wherein the immunogenic portion of the influenza virus HA protein is a receptor binding domain (RBD); the immunogenic portion in each species of self-assembling fusion protein differs from the immunogenic portion in the other species of self-assembling fusion proteins by at least one amino acid; the fusion proteins self-assemble to form a nanoparticle that displays on its surface, the immunogenic portions of the at least four species of self-assembling fusion proteins; at least one of the species of self-assembling fusion proteins comprises an amino acid sequence at least 80% identical to SEQ ID NO: 97; and the cell is cultured under conditions suitable for expressing the encoded self-assembling fusion proteins to form the nanoparticle.

8 . The method of claim 7 , wherein at least one of the species of self-assembling fusion proteins comprises an amino acid sequence at least 90% identical to SEQ ID NO: 97.

9 . The method of claim 7 , wherein at least one of the species of self-assembling fusion proteins comprises an amino acid sequence at least 95% identical to SEQ ID NO: 97.

10 . The method of claim 7 , wherein at least one of the species of self-assembling fusion proteins comprises an amino acid sequence at least 99% identical to SEQ ID NO: 97.

11 . The method of claim 7 , wherein the at least one species of self-assembling fusion protein comprises an amino acid sequence set forth as SEQ ID NO:97, SEQ ID NO:100, SEQ ID NO:103, SEQ ID NO: 106, SEQ ID NO: 109, SEQ ID NO:112, SEQ ID NO:115, SEQ ID NO:118, SEQ ID NO:121, SEQ ID NO:124, SEQ ID NO:127, SEQ ID NO:130, SEQ ID NO:133, SEQ ID NO:136, SEQ ID NO:139, or SEQ ID NO:142.

12 . The method of claim 7 , wherein the at least one species of self-assembling fusion protein comprises an amino acid sequence set forth as SEQ ID NO: 97.

Assignees

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

Inventors

• Graham Barney S
• Kanekiyo Masaru
• Yassine Hadi M

Classifications

• Y02A50/30

  Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change · CPC title

• C12N2760/16171

  Demonstrated in vivo effect · CPC title

• 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

• A61K2039/70

  Multivalent vaccine · CPC title

• A61K2039/575

  humoral response · CPC title