Virus-like particles and methods of use

Patent metadata

Field	Value
Publication number	US-11718647-B2
Application number	US-202117410182-A
Country	US
Kind code	B2
Filing date	Aug 24, 2021
Priority date	Jan 31, 2011
Publication date	Aug 8, 2023
Grant date	Aug 8, 2023

Abstract

The invention features modified alphavirus or flavivirus virus-like particles (VLPs). The invention provides methods, compositions, and kits featuring the modified VLPs. The invention also features methods for enhancing production of modified VLPs for use in the prevention or treatment of alphavirus and flavivirus-mediated diseases. The invention also provides methods for delivering agents to a cell using the modified VLPs.

First claim

What is claimed is:

1. A method, comprising:
administering to a subject a virus-like particle (VLP) comprising at least one altered viral protein as follows:
a. an alphavirus E2 protein comprising one or more alterations, relative to the wild-type amino acid sequence, at one or more amino acid locations corresponding to one or more amino acid locations selected from the group consisting of amino acid 170, amino acid 200, amino acid 233, amino acid 234, amino acid 251, and amino acid 256 of Chikungunya virus (CHIKV) E2 protein; and
b. an alphavirus capsid protein comprising one or more alterations, relative to the wild-type amino acid sequence, at a charged amino acid residue in the Nuclear Localization Signal (NLS); and
wherein the at least one altered viral protein is capable of self-assembling into a VLP;
wherein the one or more alterations enhance VLP production; and
wherein the VLP is administered to the subject in an amount effective to induce an immune response in the subject that inhibits infection with the alphavirus.

2. The method of claim 1 , wherein the alphavirus is selected from Eastern equine encephalitis virus (EEEV), Western equine encephalitis virus (WEEV), Venezuelan equine encephalitis virus (VEEV), Semliki Forest virus (SFV), Chikungunya virus (CHIKV), O'nyong-nyong virus, Sindbis virus, Mayaro virus, Ross River virus, Barmah Forest virus, and Ockelbo virus.

3. The method of claim 2 , wherein the alphavirus is selected from Eastern equine encephalitis virus (EEEV), Western equine encephalitis virus (WEEV), and Venezuelan equine encephalitis virus (VEEV).

4. The method of claim 1 , wherein the one or more alterations in a charged amino acid residue in the NLS is in at least one amino acid region selected from:
a. amino acids 67-70 of an EEEV capsid protein;
b. amino acids 67-70 of an WEEV capsid protein;
c. amino acids 64-68 of an VEEV capsid protein;
d. amino acids 62-69 of a CHIKV capsid protein;
e. amino acids 71-74 of a Ross River virus capsid protein; and
f. amino acids 64-68 of a Barmah Forest virus capsid protein.

5. The method of claim 4 , wherein the one or more alteration in a charged amino acid residue in the NLS is in at least one amino acid region selected from:
a. amino acids 67-70 of an EEEV capsid protein;
b. amino acids 67-70 of an WEEV capsid protein; and
c. amino acids 64-68 of an VEEV capsid protein.

6. The method of claim 1 , comprising administering to the subject a combination of VLPs comprising at least one of the altered viral proteins.

7. The method of claim 6 , wherein the combination of VLPs comprises VLPs comprising at least one altered viral protein from Eastern equine encephalitis virus (EEEV), Western equine encephalitis virus (WEEV), and Venezuelan equine encephalitis virus (VEEV).

8. The method of claim 1 , wherein administration of the virus-like particle protects against viremia or the inflammatory consequences of an alphavirus infection.

9. The method of claim 1 , wherein the method induces neutralizing antibodies to the alphavirus in the subject.

10. The method of claim 1 , wherein the immune response prevents infection with the alphavirus in the subject.

11. The method of claim 1 , wherein in one or more doses of the VLP are administered to the subject to induce the immune response.

12. The method of claim 11 , wherein the VLP is administered in one or more priming immunizations and one or more boosting immunizations.

13. The method of claim 1 , wherein the VLP is administered to the subject with an adjuvant.

14. The method of claim 13 , wherein the adjuvant is alum.

Assignees

• Us Health

Inventors

• Nabel Gary J
• Rao Srinivas
• Akahata Wataru

Classifications

• C07K14/005 Primary

  from viruses · CPC title

• A61K39/12 Primary

  Viral antigens · 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

• A61K2039/5258

  Virus-like particles · CPC title

• A61K2039/53

  DNA (RNA) vaccination · CPC title