Recombinant bicistronic flavivirus vectors
This invention relates to bicistronic flavivirus vectors, methods of using such vectors in the prevention and treatment of disease, and methods of making such vectors.
1. A method of administering a protein or peptide to a subject, the method comprising administering to the subject a chimeric flavivirus comprising structural sequences of a first flavivirus and non-structural sequences of a yellow fever virus, wherein the genome of said chimeric flavivirus comprises an internal ribosome entry site and a transgene located in the 3′-untranslated region of the flavivirus.
2. The method of claim 1 , wherein the chimeric flavivirus comprises pre-membrane and envelope sequences of said first flavivirus, and capsid and non-structural sequences of said yellow fever virus.
3. The method of claim 1 , wherein the first flavivirus is selected from the group consisting of Japanese encephalitis, Dengue-1, Dengue-2, Dengue-3, Dengue-4, Murray Valley encephalitis, St. Louis encephalitis, West Nile, Kunjin, Rocio encephalitis, Ilheus, Tick-borne encephalitis, Central European encephalitis, Siberian encephalitis, Russian Spring-Summer encephalitis, Kyasanur Forest Disease, Omsk Hemorrhagic fever, Louping ill, Powassan, Negishi, Absettarov, Hansalova, Apoi, and Hypr viruses.
4. The method of claim 1 , wherein the first flavivirus is a Japanese encephalitis virus.
5. The method of claim 1 , wherein the flavivirus comprises a deletion within the 3′-untranslated region of the flavivirus.
6. The method of claim 1 , wherein the transgene encodes a vaccine antigen.
7. The method of claim 6 , wherein the vaccine antigen is derived from an infectious agent.
8. The method of claim 7 , wherein the infectious agent is an influenza virus.
9. The method of claim 8 , wherein the vaccine antigen is selected from the group consisting of hemagglutinin, neuraminidase, or an immunogenic fragment thereof.
10. The method of claim 6 , wherein the vaccine antigen is a tumor-associated antigen.
11. A nucleic acid molecule encoding a chimeric flavivirus comprising structural sequences of a first flavivirus and non-structural sequences of a yellow fever virus, wherein the genome of said chimeric flavivirus comprises an internal ribosome entry site and a transgene located in the 3′-untranslated region of the chimeric flavivirus.
12. The nucleic acid molecule of claim 11 , wherein the transgene encodes an influenza antigen or an immunogenic fragment thereof.