IP Library › Granted Patent US 11,406,699
Granted Patent B2
US 11,406,699 · App. 16/820,462 · Granted Aug 9, 2022

Alphavirus and compositions, methods, and kits related thereto

Inventors: Kylene Wesley Kehn-Hall (Fredericksburg, VA); Brian D. Carey (Manassas Park, VA); Ivan V. Akhrymuk (Gainesville, VA); Caitlin W. Lehman (Manassas, VA)
Assignee: George Mason University
A61K39/12C12N15/86A61K2039/5254C12N2770/36134C12N2770/36141
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Quick Facts
Patent No.
US 11,406,699
App. No.
16/820,462
Granted
Aug 9, 2022
Kind
B2
Abstract

The present invention provides modified alphaviruses and compositions, methods, and kits for preparing and using them to elicit an immune response to an alphavirus in a subject.

Claims (14)

1. An alphavirus having a capsid protein comprising a modification to decrease phosphorylation of the capsid protein compared to a nonmodified capsid,

wherein the alphavirus is a live, attenuated VEEV virus,

the modification prevents phosphorylation of one or more amino acid residues of the capsid protein by a serine/threonine kinase, and

the modification comprises one or more substitutions at amino acid residues corresponding to positions T93, T108, S124, and/or T127, or equivalent position, of SEQ ID NO:1.

2. The alphavirus of claim 1 , wherein the serine/threonine kinase is a PKGδ.

3. The alphavirus of claim 1 , wherein the alphavirus is capable of replication, wherein pathogenicity of the virus is reduced compared to a control virus comprising the nonmodified capsid, and wherein administration of the virus to a subject elicits an immune response.

4. The alphavirus of claim 1 , wherein the capsid protein comprises the amino acid sequence as set forth in SEQ ID NO:10.

5. A composition comprising the alphavirus of claim 1 ; and a pharmaceutically acceptable carrier.

6. An isolated host cell comprising the alphavirus of claim 1 .

7. A kit comprising the alphavirus of claim 1 .

8. A method for eliciting an immune response in a subject against VEEV, the method comprises administering to the subject a prophylactically or therapeutically effective amount of the alphavirus of claim 1 .

9. A method for preparing the live, attenuated VEEV alphavirus of claim 1 , the method comprising

providing a modified alphavirus having a genome capable of expressing a modified capsid protein comprising a modification relative to a nonmodified capsid of a wild-type alphavirus genome, wherein the modification decreases phosphorylation of the modified capsid protein compared to the nonmodified capsid.

10. The method of claim 9 , wherein the modified capsid protein has the amino acid sequence as set forth in SEQ ID NO:10.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 24, 2020
From: KEHN-HALL, KYLENE WESLEY; CAREY, BRIAN D.; AKHRYMUK, IVAN V.; LEHMAN, CAITLIN W.
To: GEORGE MASON UNIVERSITY
Reel/Frame 052211/0717 →
Continuity (2)
Provisional Application 62822498 · Mar 22, 2019
Related Publication 20200297834A1 · Sep 24, 2020
Cited By (4)
US 12,233,160 US 12,257,299 US 12,350,329 US 12,433,957