IP Library › Granted Patent US 12,370,249
Granted Patent B2
US 12,370,249 · App. 18/394,555 · Granted Jul 29, 2025

Replication-deficient modified vaccinia ankara (MVA) expressing marburg virus glycoprotein (GP) and matrix protein (VP40)

Inventors: Harriet Robinson (Palo Alto, CA); Arban Domi (Atlanta, GA); Michael Hellerstein (Atlanta, GA)
Assignee: GeoVax, Inc.
A61K39/12C12N15/86C12N15/863A61K2039/5256A61K2039/5258C12N2710/24141C12N2710/24143C12N2760/10034C12N2760/14134C12N2760/14234
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Quick Facts
Patent No.
US 12,370,249
App. No.
18/394,555
Granted
Jul 29, 2025
Kind
B2
Abstract

The compositions and methods are described for generating an immune response to a hemorrhagic fever virus such as ebolavirus, Marburgvirus , or arenavirus. The compositions and methods described herein relate to a modified vaccinia Ankara (MVA) vector encoding one or more viral antigens for generating a protective immune response to a member of genus Ebolavirus (such as a member of species Zaire ebolavirus ), a member of genus Marburgvirus (such as a member of species Marburg marburgvirus ), or a member of genus Arenavirus (such as a member of species Lassa virus ) in the subject to which the vector is administered. The compositions and methods of the present invention are useful both prophylactically and therapeutically and may be used to prevent and/or treat an infection caused by ebolavirus, Marburgvirus , or arenavirus.

Claims (54)

1. A method of preventing an infection by a Marburg virus in a human subject at risk of exposure thereto, said method comprising administering to the human subject in need thereof a pharmaceutical composition in a prophylactically effective amount, wherein the pharmaceutical composition comprises:

a) a recombinant modified vaccinia ankara (MVA) vector comprising:

i) a first nucleic acid encoding a Marburg virus (MARV) glycoprotein, and

ii) a second nucleic acid sequence encoding a Marburg virus (MARV) VP40 matrix protein;

wherein both the first nucleic acid sequence and the second nucleic acid sequence are under the control of one or more promoters compatible with poxvirus expression systems;

wherein the first nucleic acid is located between MVA genes I8R and GIL;

wherein the second nucleic acid sequence is located between MVA genes A50R and BIR in a restructured and modified deletion site III; and

wherein the MARV glycoprotein and the MARV VP40 matrix protein are capable of assembling into virus-like particles (VLPs) when expressed in a host cell; and

b) a pharmaceutically acceptable carrier.

2. The method of claim 1 , wherein the first nucleic acid sequence and the second nucleic acid sequence are optimized by one or more method selected from the group consisting of i) changing selected codons to other synonymous codons that are optimal for protein expression by MVA, ii) interrupting homopolymer stretches using silent mutations, and iii) interrupting transcription terminator motifs using silent mutations.

3. The method of claim 1 , wherein the MARV glycoprotein and MARV VP40 matrix protein are derived from the same MARV strain.

4. The method of claim 1 , wherein the first nucleic acid sequence comprises nucleic acids 1631-3676 of SEQ ID NO: 15, or a nucleic acid sequence at least 95% identical thereto.

5. The method of claim 1 , wherein the first nucleic acid sequence comprises nucleic acids 1631-3676 of SEQ ID NO: 15.

6. The method of claim 1 , wherein the second nucleic acid sequence comprises nucleic acids 1581-2492 of SEQ ID NO: 14, or a nucleic acid sequence at least 95% identical thereto.

7. The method of claim 1 , wherein the second nucleic acid sequence comprises nucleic acids 1581-2492 of SEQ ID NO: 14.

8. The method of claim 1 , wherein the first nucleic acid sequence comprises nucleic acids 1631-3676 of SEQ ID NO: 15, and the second nucleic acid sequence comprises nucleic acids 1581-2492 of SEQ ID NO: 14.

9. The method of claim 1 , wherein the administration is repeated at least twice.

10. A method of preventing an infection by a Marburg virus in a human subject at risk of exposure thereto, said method comprising administering to the human subject in need thereof a pharmaceutical composition in a prophylactically effective amount, wherein the pharmaceutical composition comprises:

a) a recombinant modified vaccinia ankara (MVA) vector comprising:

i) a first nucleic acid sequence encoding a Marburg virus glycoprotein comprising nucleic acids 1631-3676 of SEQ ID NO: 15, or a nucleic acid sequence at least 95% identical thereto, and

ii) a second nucleic acid sequence encoding a Marburg virus VP40 matrix protein comprising nucleic acids 1581-2492 of SEQ ID NO: 14, or a nucleic acid sequence at least 95% identical thereto;

wherein both the first nucleic acid sequence and the second nucleic acid sequence are under the control of one or more promoters compatible with poxvirus expression systems;

wherein the first nucleic acid is located between MVA genes I8R and GIL;

wherein the second nucleic acid sequence is located between MVA genes A50R and BIR in a restructured and modified deletion site III; and

wherein the Marburg virus glycoprotein and the Marburg virus VP40 matrix protein are capable of assembling into virus-like particles (VLPs) when expressed in a host cell; and

b) a pharmaceutically acceptable carrier.

11. The method of claim 10 , wherein the administration is repeated at least twice.

12. A method of inducing an immune response to a Marburg virus in a human subject at risk of exposure thereto, said method comprising administering to the human subject in need thereof a pharmaceutical composition in a prophylactically effective amount, wherein the pharmaceutical composition comprises:

a) at least one recombinant modified vaccinia ankara (MVA) vector comprising:

i) a first nucleic acid encoding a Marburg virus (MARV) glycoprotein, and

ii) a second nucleic acid sequence encoding a Marburg virus (MARV) VP40 matrix protein;

wherein both the first nucleic acid sequence and the second nucleic acid sequence are under the control of one or more promoters compatible with poxvirus expression systems;

wherein the first nucleic acid is located between MVA genes I8R and GIL;

wherein the second nucleic acid sequence is located between MVA genes A50R and BIR in a restructured and modified deletion site III; and

wherein the MARV glycoprotein and the MARV VP40 matrix protein are capable of assembling into virus-like particles (VLPs) when expressed in a host cell; and

b) a pharmaceutically acceptable carrier.

13. The method of claim 12 , wherein the first nucleic acid sequence and the second nucleic acid sequence are optimized by one or more method selected from the group consisting of i) changing selected codons to other synonymous codons that are optimal for protein expression by MVA, ii) interrupting homopolymer stretches using silent mutations, and iii) interrupting transcription terminator motifs using silent mutations.

14. The method of claim 12 , wherein the MARV glycoprotein and MARV VP40 matrix protein are derived from the same MARV strain.

15. The method of claim 12 , wherein the first nucleic acid sequence comprises nucleic acids 1631-3676 of SEQ ID NO: 15, or a nucleic acid sequence at least 95% identical thereto.

16. The method of claim 12 , wherein the first nucleic acid sequence comprises nucleic acids 1631-3676 of SEQ ID NO: 15.

17. The method of claim 12 , wherein the second nucleic acid sequence comprises nucleic acids 1581-2492 of SEQ ID NO: 14, or a nucleic acid sequence at least 95% identical thereto.

18. The method of claim 12 , wherein the second nucleic acid sequence comprises nucleic acids 1581-2492 of SEQ ID NO: 14.

19. The method of claim 12 , wherein the first nucleic acid sequence comprises nucleic acids 1631-3676 of SEQ ID NO: 15, and the second nucleic acid sequence comprises nucleic acids 1581-2492 of SEQ ID NO:14.

20. The method of claim 12 , wherein the administration is repeated at least twice.

21. A method of inducing an immune response to a Marburg virus in a human subject at risk of exposure thereto, said method comprising administering to the human subject in need thereof a pharmaceutical composition in a prophylactically effective amount, wherein the pharmaceutical composition comprises:

a) a recombinant modified vaccinia ankara (MVA) vector comprising:

i) a first nucleic acid sequence encoding a Marburg virus glycoprotein comprising nucleic acids 1631-3676 of SEQ ID NO: 15, or a nucleic acid sequence at least 95% identical thereto, and

ii) a second nucleic acid sequence encoding a Marburg virus VP40 matrix protein comprising nucleic acids 1581-2492 of SEQ ID NO: 14, or a nucleic acid sequence at least 95% identical thereto;

wherein both the first nucleic acid sequence and the second nucleic acid sequence are under the control of one or more promoters compatible with poxvirus expression systems;

wherein the first nucleic acid is located between MVA genes I8R and GIL;

wherein the second nucleic acid sequence is located between MVA genes A50R and BIR in a restructured and modified deletion site III; and

wherein the Marburg virus glycoprotein and the Marburg virus VP40 matrix protein are capable of assembling into virus-like particles (VLPs) when expressed in a host cell; and

b) a pharmaceutically acceptable carrier.

22. The method of claim 21 , wherein the administration is repeated at least twice.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 3, 2025
From: DOMI, ARBAN; HELLERSTEIN, MICHAEL; ROBINSON, HARRIET
To: GEOVAX, INC.
Reel/Frame 070729/0654 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 3, 2025
From: DOMI, ARBAN; HELLERSTEIN, MICHAEL; ROBINSON, HARRIET
To: GEOVAX, INC.
Reel/Frame 070729/0681 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 3, 2025
From: DOMI, ARBAN; HELLERSTEIN, MICHAEL; ROBINSON, HARRIET
To: GEOVAX, INC.
Reel/Frame 070739/0581 →
Continuity (6)
Continuation 17584231 · Jan 25, 2022
Continuation 15543139
Provisional Application 62215536 · Sep 8, 2015
Provisional Application 62213819 · Sep 3, 2015
Provisional Application 62102425 · Jan 12, 2015
Related Publication 20240156940A1 · May 16, 2024
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