IP Library › Granted Patent US 12,442,018
Granted Patent B2
US 12,442,018 · App. 18/496,076 · Granted Oct 14, 2025

Recombinant cytomegalovirus vectors as vaccines for tuberculosis

Inventors: Thomas G. Evans (New York, NY); Ravi Anantha (New York, NY); Aurelio M. Bonavia (New York, NY); Dominick J. Laddy (New York, NY); Louis Picker (Beaverton, OR); Scott Hansen (Beaverton, OR); Guangwu Xu (Beaverton, OR)
Assignees: International AIDS Vaccine Initiative, Inc.; Oregon Health and Science University
C12N15/86A61K39/04C07K14/35A61K2039/5256A61K2039/53C07K2319/00C12N2710/16143C12N2710/16151C12N2710/16171C12N2800/204C12N2800/30
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Quick Facts
Patent No.
US 12,442,018
App. No.
18/496,076
Granted
Oct 14, 2025
Kind
B2
Abstract

Provided are cytomegalovirus vectors encoding fusion proteins comprising Mycobacterium tuberculosis (Mtb) antigens, nucleic acid molecules encoding the same, cytomegalovirus vectors comprising nucleic acid molecules, compositions comprising the same, and methods of eliciting an immune response against tuberculosis.

Claims (17)

1. A method of preparing a rhesus cytomegalovirus (RhCMV) or a human cytomegalovirus (HCMV) vaccine vector comprising a nucleic acid sequence encoding an expressible Mycobacterium tuberculosis (Mtb) antigen, the method comprising:

i) inserting into a RhCMV genome or a HCMV genome a nucleic acid sequence encoding an expressible Mtb antigen consisting of Ag85A-Ag85B-Rv3407, Rv1733-Rv2626c, and Ag85A-ESAT6-Rv3407-Rv2626c-RpfA-RpfD; and

ii) attenuating the RhCMV genome or the HCMV genome.

2. The method of claim 1 , wherein attenuating comprises disabling a gene that is essential for replication within a host, dissemination within a host, or spreading from host to host.

3. The method of claim 1 , wherein attenuating comprises deleting or modifying of US2, US3, US4, US5, US6, US11, or UL97, or a homolog thereof.

4. The method of claim 1 , wherein attenuating comprises deleting or modifying of Rh158-166 or a homolog thereof.

5. The method of claim 1 , wherein the RhCMV or HCMV vaccine vector is a tropism-restricted vector that lacks genes required for optimal growth in certain cell types or contains targets for tissue-specific micro-RNAs in genes essential for viral replication or wherein the tropism-restrictive vector has an epithelial, central nervous system (CNS), or macrophage deficient tropism, or a combination thereof.

6. The method of claim 1 , wherein attenuating comprises deleting a gene region non-essential for growth in vivo.

7. The method of claim 6 , wherein the gene region non-essential for growth in vivo is selected from the group consisting of the RL11 family, the pp65 family, the US12 family, and the US28 family.

8. The method of claim 7 , wherein the gene region is selected from the group consisting of the RL11 family, the pp65 family, the US12 family, and the US28 family.

9. The method of claim 8 , wherein the RhCMV gene region is selected from the group consisting of Rh13-Rh29, Rh111-Rh112, Rh191-Rh202, and Rh214-Rh220, or wherein the RhCMV gene region is selected from the group consisting of Rh13.1, Rh19, Rh20, Rh23, Rh24, Rh112, Rh190, Rh192, Rh196, Rh198, Rh199, Rh200, Rh201, Rh202, and Rh220.

10. The method of claim 1 , wherein attenuating comprises a deletion in gene UL82 or a homolog thereof.

11. The method of claim 1 , wherein attenuating comprises inserting into the vaccine vector a nucleic acid sequence encoding US2, US3, or US6, or a homolog thereof, wherein the vector does not encode a functional US11.

12. The method of claim 11 , wherein the nucleic acid sequence encodes US2, US3, and US6.

13. The method of claim 11 , wherein attenuating comprises inserting into the vaccine vector a nucleic acid sequence encoding US11, and wherein the nucleic acid sequence encoding US11 comprises a point mutation, a frameshift mutation, and/or a deletion of one or more nucleotides of the nucleic acid sequence encoding US11.

14. The method of claim 1 , wherein the RhCMV vaccine vector is Rh68-1 or Rh68-1.2.

15. The method of claim 1 , wherein the RhCMV or HCMV vaccine vector further comprises a microRNA recognition element (MRE) operably linked to a CMV gene that is essential or augmenting for CMV growth, and wherein the MRE silences expression in the presence of a microRNA that is expressed by a cell of myeloid lineage.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 5, 2024
From: EVANS, THOMAS G.; ANANTHA, RAVI P.; BONAVIA, AURELIO M.; LADDY, DOMINICK J.
To: AERAS
Reel/Frame 066032/0585 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 5, 2024
From: AERAS
To: INTERNATIONAL AIDS VACCINE INITIATIVE, INC.
Reel/Frame 066033/0120 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 5, 2024
From: PICKER, LOUIS; HANSEN, SCOTT; XU, GUANGWU
To: OREGON HEALTH AND SCIENCE UNIVERSITY
Reel/Frame 066033/0755 →
Continuity (5)
Continuation 17365509 · Jul 1, 2021
Continuation 15628921 · Jun 21, 2017
Provisional Application 62478099 · Mar 29, 2017
Provisional Application 62353432 · Jun 22, 2016
Related Publication 20240150789A1 · May 9, 2024
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