Recombinant isfahan viral vectors

Patent metadata

Field	Value
Publication number	US-9932564-B2
Application number	US-201515122695-A
Country	US
Kind code	B2
Filing date	Feb 27, 2015
Priority date	Mar 1, 2014
Publication date	Apr 3, 2018
Grant date	Apr 3, 2018

Abstract

Certain embodiments are directed to recombinant vesiculovirus encoding a heterologous polynucleotide and methods of using the same.

First claim

The invention claimed is:

1. A recombinant replication competent Isfahan virus comprising an N protein gene, a P protein gene, an M protein gene, a G protein gene, and an L protein gene; and further comprising a heterologous polynucleotide sequence encoding a heterologous polypeptide.

2. The Isfahan virus of claim 1 , wherein the heterologous polynucleotide sequence is flanked by a transcription start signal and a transcription stop signal.

3. The Isfahan virus of claim 1 , wherein the heterologous polynucleotide encodes an immunogenic polypeptide.

4. The Isfahan virus of claim 1 , wherein the heterologous polynucleotide encodes one or more antigens.

5. The Isfahan virus of claim 4 , wherein the antigen is a viral antigen, a bacterial antigen, a tumor-specific or cancer antigen, a parasitic antigen or an allergen.

6. The Isfahan virus of claim 5 , wherein the antigen is a viral antigen.

7. The Isfahan virus of claim 1 , wherein the heterologous polynucleotide sequence is located at position 1, 2, 3, 4, 5 or 6 of the Isfahan virus genome.

8. The Isfahan virus of claim 1 , wherein the N protein gene is located at position 1, 2, 3, 4 or 5 of the Isfahan virus genome.

9. The Isfahan virus of claim 1 , wherein the G protein gene encodes a G protein having a carboxy-terminal truncation.

10. The Isfahan virus of claim 9 , wherein the G protein has a carboxy-terminal truncation of 20 to 25 amino acids.

11. The Isfahan virus of claim 1 , wherein the heterologous polynucleotide sequence is located at position 5 and the N protein gene is located at position 4 of the Isfahan virus genome.

12. An isolated host cell comprising the Isfahan virus of claim 1 .

13. An immunogenic composition comprising a recombinant replication competent Isfahan virus comprising an N protein gene, a P protein gene, an M protein gene, a G protein gene, and an L protein gene; and further comprising a heterologous polynucleotide sequence, wherein said heterologous polynucleotide sequence encodes a heterologous polypeptide; and a pharmaceutically acceptable diluent, excipient or carrier.

14. The immunogenic composition of claim 13 , wherein the heterologous polynucleotide sequence is flanked by a transcription start signal and a transcription stop signal.

15. A method of inducing an antigen-specific immune response to an antigen in a mammalian subject comprising administering the immunogenic composition of claim 14 .

16. An immunization kit for inducing an antigen-specific immune response in a mammalian subject, said kit comprising:
(a) a priming composition comprising a recombinant replication competent Isfahan virus encoding an N protein gene, a P protein gene, an M protein gene, a G protein gene, an L protein gene, and a heterologous polynucleotide sequence, wherein said heterologous polynucleotide sequence encodes a heterologous polypeptide, wherein said heterologous polynucleotide sequence (i) is flanked by a transcription start signal and a transcription stop signal, and (ii) encodes a heterologous polypeptide; and a pharmaceutically acceptable diluent, excipient or carrier; and
(b) a boosting composition comprising a recombinant replication competent vesicular stomatitis virus encoding an N protein gene, a P protein gene, an M protein gene, a G protein gene, an L protein gene, and a heterologous polynucleotide sequence, wherein said heterologous polynucleotide sequence (i) is flanked by a transcription start signal and a transcription stop signal, and (ii) encodes a heterologous polypeptide; and a pharmaceutically acceptable diluent, excipient or carrier.

17. A method of inducing an antigen-specific immune response in a mammalian subject comprising administering the immunogenic compositions of claim 16 .

18. An immunization kit for inducing an antigen-specific immune response in a mammalian subject, said kit comprising:
(a) a priming composition comprising a recombinant replication competent vesicular stomatitis virus (VSV) encoding an N protein gene, a P protein gene, an M protein gene, a G protein gene, an L protein gene, and a heterologous polynucleotide sequence, wherein said heterologous polynucleotide sequence encodes a heterologous polypeptide, wherein said heterologous polynucleotide sequence (i) is flanked by a transcription start signal and a transcription stop signal, and (ii) encodes a heterologous polypeptide; and a pharmaceutically acceptable diluent, excipient or carrier; and
(b) a boosting composition comprising a recombinant replication competent Isfahan virus (ISFV) encoding an N protein gene, a P protein gene, an M protein gene, a G protein gene, an L protein gene, and a heterologous polynucleotide sequence, wherein said heterologous polynucleotide sequence encodes a heterologous polypeptide, wherein said heterologous polynucleotide sequence (i) is flanked by a transcription start signal and a transcription stop signal, and (ii) encodes a heterologous polypeptide; and a pharmaceutically acceptable diluent, excipient or carrier.

19. A method of inducing an antigen-specific immune response in a mammalian subject comprising administering the immunogenic compositions of claim 18 .

20. A recombinant replication competent Isfahan virus comprising an N protein gene, a P protein gene, an M protein gene, a heterologous viral surface protein gene(s), and an L protein gene.

21. The recombinant replication competent Isfahan virus of claim 20 , further comprising a second heterologous polynucleotide sequence, wherein said heterologous polynucleotide sequence encodes a second heterologous polypeptide.

22. The recombinant replication competent Isfahan virus of claim 20 , wherein the heterologous viral surface protein gene replaces the Isfahan virus G protein gene.

23. The recombinant replication competent Isfahan virus of claim 20 , wherein the heterologous viral surface protein gene is a G protein gene of vesicular stomatitis virus.

24. An oncolytic viral composition comprising a recombinant replication competent Isfahan virus comprising an N protein gene, a P protein gene, an M protein gene, a G protein gene, and an L protein gene, wherein said Isfahan virus is used as an anti-cancer therapeutic.

25. The Isfahan virus of claim 6 , wherein the viral antigen is from Chikungunya virus.

Assignees

• Univ Texas
• Profectus Biosciences Inc

Inventors

• Matassov Demetrius
• Gorchakov Rodion V
• Hamm Stefan
• Nowak Rebecca
• Seymour Robert L
• Eldridge John H
• Tesh Robert B
• Clarke David K
• Latham Theresa E
• Weaver Scott
• Nasar Farooq

Classifications

• A61P37/04

  Immunostimulants · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C12N2770/36134

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

• A61K2039/545

  characterised by the dose, timing or administration schedule · CPC title

• C12N2740/16071

  Demonstrated in vivo effect · CPC title