Chimeric norovirus P particle and preparation and use thereof

Patent metadata

Field	Value
Publication number	US-11116831-B2
Application number	US-201615744585-A
Country	US
Kind code	B2
Filing date	Jun 29, 2016
Priority date	Jul 15, 2015
Publication date	Sep 14, 2021
Grant date	Sep 14, 2021

Abstract

Provided is a recombinant P particle formed from a norovirus capsid P protein of a chimeric Aβ1-m peptide (m being an integer ranging from 6 to 15), wherein the recombinant P particles form an ordered and repetitive antigen array. Also provided are a nucleotide sequence encoding the recombinant P particle, a pharmaceutical composition comprising same and a use thereof for preparing a medicament for treating or preventing Alzheimer's disease. Also provided is a method for preparing the recombinant P particle.

First claim

The invention claimed is:

1. A recombinant P particle formed from a norovirus capsid P protein chimerized with a Aβ1-m peptide, wherein m is an integer ranging from 6 to 15, and the recombinant P particle forms an ordered and repetitive antigen array, and the amino acid sequence of at least one of the Aβ1-m peptides is embedded into loop1, loop2 and/or loop3 of the norovirus capsid P protein,
wherein the amino acid sequence of the norovirus capsid P protein comprises the sequence of SEQ ID NO: 1, and
wherein N1 Aβ1-m peptide sequences are embedded behind one or more amino acid sites selected from the group consisting of amino acids 70-74 of SEQ ID NO: 1, i.e. 170, A71, G72, T73 and Q74; N2 Aβ1-m peptide sequences are embedded behind one or more amino acid sites selected from the group consisting of amino acids 148-151 of SEQ ID NO: 1, i.e. T148, S149, N150 and D151; and N3 Aβ1-m peptide sequences are embedded behind one or more amino acid sites selected from the group consisting of amino acids 168-171 of SEQ ID NO: 1, i.e. D168, G169, S170 and T171; wherein N1, N2 and N3 each are independently selected from an integer ranging from 0-40, and N1+N2+N3≥1.

2. The recombinant P particle according to claim 1 , wherein multiple consecutive Aβ1-m peptide sequences embedded into the norovirus capsid P protein are linked directly or via a polypeptide linker.

3. The recombinant P particle according to claim 1 , wherein the Aβ1-m peptide is linked to the norovirus capsid P protein directly or via a polypeptide linker.

4. The recombinant P particle according to claim 1 , wherein the Aβ1-m peptide sequence is an amino acid sequence comprised in sequences selected from SEQ ID NOs: 2-8.

5. The recombinant P particle according to claim 1 , wherein the chimerized norovirus capsid P protein is encoded by nucleic acid sequences of SEQ ID NO: 15-SEQ ID NO: 141.

6. A nucleic acid encoding the recombinant P particle according to claim 1 , wherein the nucleic acid has sequences of SEQ ID NO: 15-SEQ ID NO: 141.

7. A pharmaceutical composition used for preventing or treating Alzheimer's disease, comprising the recombinant P particle according to claim 1 and a pharmaceutically acceptable carrier.

8. Use of the recombinant P particle according to claim 1 in the manufacture of a medicament for treating or preventing Alzheimer's disease, wherein the medicament is a vaccine.

9. A method for preparing the recombinant P particle according to claim 1 , comprising the following steps:
i) obtaining an expression vector comprising a nucleic acid encoding a norovirus capsid P protein chimerized with a Aβ1-m peptide, wherein m is an integer ranging from 6 to 15;
ii) transferring the expression vector into a receptor cell;
iii) expressing the chimerized norovirus capsid P protein, and allowing it to self-assemble into a recombinant P particle.

Assignees

• Changchun Bcht Biotechnology Co
• Univ Jilin

Inventors

• Kong Wei
• Wu Hui
• Jiang Chunlai
• Yu Xianghui
• Fu Lu
• Li Yingnan

Classifications

• A61K39/00

  Medicinal preparations containing antigens or antibodies (materials for immunoassay G01N33/53) · CPC title

• A61P25/28 Primary

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• C12N7/04

  Inactivation or attenuation; Producing viral sub-units · CPC title

• C07K19/00

  Hybrid peptides {, i.e. peptides covalently bound to nucleic acids, or non-covalently bound protein-protein complexes} · 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