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