Use of oil and water emulsions for increasing B cell responses with modified Vaccinia Ankara virus

Patent metadata

Field	Value
Publication number	US-10653766-B2
Application number	US-201515125388-A
Country	US
Kind code	B2
Filing date	Mar 12, 2015
Priority date	Mar 12, 2014
Publication date	May 19, 2020
Grant date	May 19, 2020

Abstract

The invention relates to compositions, uses, and methods for inducing an immune response against a vaccinia virus. The addition of an oil and water emulsion to MVA can vastly increase the B cell response and particularly neutralizing antibodies against vaccinia virus and encoded recombinant antigens. Thus, the addition of an oil and water emulsion to MVA can increase the protective immune response. The invention encompasses administering a dose of an MVA in an oil and water emulsion to an animal, especially a human.

First claim

The invention claimed is:

1. A pharmaceutical composition for inducing vaccinia neutralizing antibodies in an animal comprising a dose of at least 2×10 7 TCID 50 of a recombinant modified vaccinia Ankara (MVA) virus comprising a nucleic acid sequence encoding an antigen selected from the group consisting of:
(a) an antigen of a yellow fever virus; and
(b) an antigen of RSV

in an emulsion comprising oil and water, wherein the composition induces at least a 2-fold higher level of vaccinia neutralizing antibodies at 26 days after immunization when compared to the same composition in the absence of the emulsion.

2. The composition of claim 1 , wherein the composition induces at least a 5-fold higher level of vaccinia neutralizing antibodies at 35 days after immunization when compared to the same composition in the absence of the emulsion.

3. The composition of claim 2 , wherein the composition induces at least a 10-fold higher level of vaccinia neutralizing antibodies at 35 days after immunization when compared to the same composition in the absence of the emulsion.

4. The composition of claim 1 , wherein the emulsion is a water-in-oil emulsion.

5. The composition of claim 1 , wherein the emulsion is an oil-in-water emulsion.

6. The composition of claim 1 , wherein the emulsion comprises mannide monooleate.

7. The composition of claim 1 , wherein the emulsion comprises a mineral oil.

8. The composition of claim 1 , wherein the emulsion comprises a non-mineral oil.

9. The composition of claim 7 , wherein the emulsion comprises ISA 51.

10. The composition of claim 8 , wherein the emulsion comprises ISA720.

11. The composition of claim 1 , wherein the emulsion comprises squalene oil.

12. The composition of claim 11 , wherein the emulsion comprises sorbitan trioleate.

13. The composition of claim 1 that comprises a dose of between 2×10 7 TCID 50 and 1.5×10 8 TCID 50 of said recombinant MVA.

14. The composition of claim 1 , wherein the recombinant MVA comprises a nucleic acid sequence coding for an antigen of a yellow fever virus.

15. The composition of claim 13 , wherein the emulsion does not additionally contain the recombinant protein encoded by the recombinant MVA.

16. The composition of claim 1 , comprising a dose of at least 10 8 TCID 50 of an MVA.

17. The composition of claim 1 , wherein the MVA comprises a nucleotide sequence comprising at least one of SEQ ID NOs 1-6.

18. The composition of claim 1 , wherein the animal is a human.

19. A method for inducing an immune response against a modified vaccinia Ankara (MVA) virus in an animal comprising administering to the animal a dose of at least 2×10 7 TCID50 of a modified vaccinia Ankara (MVA) virus comprising a nucleic acid sequence encoding an antigen selected from the group consisting of:
(a) an antigen of a yellow fever virus; and
(b) an antigen of RSV

in an emulsion comprising oil and water, wherein the composition induces at least a 2-fold higher level of vaccinia neutralizing antibodies at 26 days after immunization when compared to the same composition in the absence of the emulsion.

20. The method of claim 19 , wherein the composition induces at least a 5-fold higher level of vaccinia neutralizing antibodies at 35 days after immunization when compared to the same composition in the absence of the emulsion.

21. The method of claim 19 , wherein the emulsion comprises ISA720.

22. A pharmaceutical composition for inducing vaccinia neutralizing antibodies in an animal comprising a dose of at least 2×10 7 TCID 50 of a recombinant modified vaccinia Ankara (MVA) virus comprising a nucleic acid sequence encoding an antigen selected from the group consisting of:
(a) an antigen of a yellow fever virus; and
(b) an antigen of RSV
in an emulsion comprising oil and water,
wherein the composition induces at least a 2-fold higher level of vaccinia neutralizing antibodies at 26 days after immunization when compared to the same composition in the absence of the emulsion inducing an immune response against a modified vaccinia Ankara (MVA) virus in an animal comprising a recombinant MVA in an oil and water emulsion, and
wherein the emulsion does not additionally contain the recombinant protein encoded by the recombinant MVA.

23. The composition of claim 22 , wherein the composition induces at least a 5-fold higher level of vaccinia neutralizing antibodies at 35 days after immunization when compared to the same composition in the absence of the emulsion.

24. The composition of claim 23 , wherein the composition induces at least a 10-fold higher level of vaccinia neutralizing antibodies at 35 days after immunization when compared to the same composition in the absence of the emulsion.

25. The composition of claim 24 , wherein the emulsion comprises ISA720.

26. The composition of claim 25 , comprising a dose of at least 10 8 TCID 50 of an MVA.

27. The composition of claim 23 , wherein the MVA comprises a nucleotide sequence comprising at least one of SEQ ID NOs 1-6.

28. The composition of claim 26 , wherein the MVA comprises a nucleotide sequence comprising at least one of SEQ ID NOs 1-5.

Assignees

• Bavarian Nordic As

Inventors

• Cheminay Cédric
• Steigerwald Robin
• Volkmann Ariane

Classifications

• A61K39/155

  Paramyxoviridae, e.g. parainfluenza virus · CPC title

• C12N2760/18534

  Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein · CPC title

• C12N2770/24134

  Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein · CPC title

• C12N2710/24121

  Viruses as such, e.g. new isolates, mutants or their genomic sequences · CPC title

• C12N2710/24143

  viral genome or elements thereof as genetic vector · CPC title