Recombinant poxvirus vector comprising tetanus toxin fragment C

Patent metadata

Field	Value
Publication number	US-9463238-B2
Application number	US-201214363287-A
Country	US
Kind code	B2
Filing date	Nov 30, 2012
Priority date	Dec 9, 2011
Publication date	Oct 11, 2016
Grant date	Oct 11, 2016

Abstract

The present invention relates to a recombinant poxvirus comprising tetanus toxin fragment C for improved immunogenicity of an antigen and related methods and uses. Specifically, the present invention generally relates to genetically engineered (recombinant) poxvirus vectors comprising a tetanus toxin fragment C (TTC) coding sequence operably linked to a bacterial antigenic determinant as well as to uses thereof, e.g., to affect an immune response in a subject.

First claim

The invention claimed is:

1. A recombinant poxvirus comprising a fusion protein coding sequence, the fusion protein comprising a tetanus toxin fragment C (TTC) and a Bacillus anthracis Protective antigen (PA) protein, wherein the coding sequence for the TTC encodes for amino acids 761-1213 of SEQ ID NO:2, and wherein the fusion protein enhances an immune response against Bacillus anthracis as compared with an immune response by a recombinant poxvirus comprising PA alone.

2. The recombinant poxvirus according to claim 1 , wherein the TTC coding sequence comprises nucleotides 2281-3642 of SEQ ID NO: 1.

3. The recombinant poxvirus according to claim 1 , wherein in the TTC is fused to the PA protein via a linker sequence.

4. The recombinant poxvirus of claim 1 , wherein the poxvirus is a vaccinia virus.

5. The recombinant poxvirus of claim 4 , wherein the vaccinia virus is a Modified Vaccinia Virus Ankara (MVA).

6. The recombinant poxvirus of claim 5 , wherein the MVA is MVA-BN.

7. The recombinant poxvirus of claim 1 , wherein the recombinant poxvirus further comprises a coding sequence for at least one Bacillus anthracis antigenic determinant selected from the group consisting of lethal factor (LF) and edema factor (EF).

8. The recombinant poxvirus according to claim 1 , further comprising a nucleic acid encoding a co-stimulatory molecule.

9. The recombinant poxvirus of claim 8 , wherein the co-stimulatory molecule is CD70, IL-12 and/or IL-15.

10. A vaccine or medicament for treating and/or preventing anthrax comprising the recombinant poxvirus of claim 6 .

11. An isolated cell comprising the recombinant poxvirus according to claim 6 .

12. A kit comprising the recombinant poxvirus according to claim 6 in a first vial or container for a first administration and in a second vial or container for a second administration.

13. A method for preventing or treating anthrax in a subject, the method comprising administering to the subject a recombinant poxvirus comprising a coding sequence for a fusion protein, the fusion protein comprising a tetanus toxin fragment C (TTC) and a Bacillus anthracis Protective antigen (PA) protein, wherein the coding sequence for the TTC encodes for amino acids 761-1213 of SEQ ID NO:2, and wherein said fusion protein enhances an immune response against Bacillus anthracis as compared with an immune response by a recombinant poxvirus comprising PA alone.

14. The method according to claim 13 , wherein the TTC coding sequence comprises nucleotides 2281-3642 of SEQ ID NO: 1.

15. The method according to claim 13 , wherein in the TTC is fused to the PA protein via a linker sequence.

16. The method of claim 13 , wherein the poxvirus is a vaccinia virus.

17. The method of claim 16 , wherein the vaccinia virus is a Modified Vaccinia Virus Ankara (MVA).

18. The method of claim 17 , wherein the MVA is MVA-BN.

19. A method of generating a recombinant poxvirus comprising a coding sequence for a fusion protein, the fusion protein comprising a tetanus toxin fragment C (TTC) and a Bacillus anthracis Protective antigen (PA) protein, wherein the coding sequence for the TTC encodes for amino acids 761-1213 of SEQ ID NO:2, and wherein said fusion protein enhances an immune response against Bacillus anthracis as compared with an immune response by a recombinant poxvirus comprising PA alone the method comprising:
a) infecting a host cell with a poxvirus;
b) transfecting the infected cell with a recombinant vector comprising the fusion protein, said vector further comprising a genomic poxvirus sequence capable of directing the integration of the TTC and antigenic determinant coding sequences into the poxvirus genome; and
c) identifying, isolating and, optionally, purifying the generated recombinant poxvirus.

Assignees

• Bavarian Nordic As

Inventors

• Chaplin Paul
• Steigerwald Robin

Classifications

• A61K39/07

  Bacillus · CPC title

• A61K2039/70

  Multivalent vaccine · CPC title

• A61K2039/5256

  expressing foreign proteins · CPC title

• A61K39/385 Primary

  Haptens or antigens, bound to carriers · CPC title

• A61K2039/6037

  Bacterial toxins, e.g. diphteria toxoid [DT], tetanus toxoid [TT] · CPC title