Flavivirus vaccines
The invention provides flavivirus vaccines and methods of making and using these vaccines.
1. A chimeric flavivirus comprising sequences encoding capsid and non-structural proteins of a yellow fever virus and pre-membrane and envelope proteins of a dengue virus selected from a dengue-1 virus, a dengue-2 virus, a dengue-3 virus, and a dengue-4 virus, wherein the dengue virus envelope protein has a substitution of the lysine in amino acid position 202 (dengue-3) or 204 (dengue-1, dengue-2, or dengue-4) with arginine.
2. The chimeric flavivirus of claim 1 , wherein said yellow fever virus is a yellow fever virus vaccine strain.
3. The chimeric flavivirus of claim 2 , wherein said yellow fever virus vaccine strain is YF17D.
4. The chimeric flavivirus of claim 1 , wherein said dengue virus is dengue-1.
5. The chimeric flavivirus of claim 1 , wherein said dengue virus is dengue-2.
6. The chimeric flavivirus of claim 1 , wherein said dengue virus is dengue-3.
7. The chimeric flavivirus of claim 1 , wherein said dengue virus is dengue-4.
8. An immunogenic composition comprising the flavivirus of claim 1 and a pharmaceutically acceptable carrier or diluent.
9. The immunogenic composition of claim 8 , wherein said composition comprises a chimera of yellow fever virus and dengue-1 virus, a chimera of yellow fever virus and dengue-2 virus, a chimera of yellow fever virus and dengue-3 virus, and a chimera of yellow fever virus and dengue-4 virus.
10. A method of inducing an immune response to a flavivirus in a patient, said method comprising administering to said patient the immunogenic composition of claim 8 .
11. The method of claim 10 , wherein said patient does not have, but is at risk of developing, said flavivirus infection.
12. The method of claim 10 , wherein said patient has said flavivirus infection.
13. The method of claim 10 , wherein the flavivirus to which an immune response is induced is a dengue virus.
14. A method of inducing an immune response to a flavivirus in a patient, said method comprising administering to said patient the immunogenic composition of claim 9 .
15. The method of claim 14 , wherein said patient does not have, but is at risk of developing, said flavivirus infection.
16. The method of claim 14 , wherein said patient has said flavivirus infection.
17. The method of claim 14 , wherein the flavivirus to which an immune response is induced is a dengue virus.
18. A method of reducing the viscerotropism and/or neurovirulence of a chimeric flavivirus comprising sequences encoding capsid and non-structural proteins of a yellow fever virus and pre-membrane and envelope proteins of a dengue virus selected from a dengue-1 virus, a dengue-2 virus, a dengue-3 virus, and a dengue-4 virus, the method comprising substituting lysine at position 202 (dengue-3) or 204 (dengue-1, dengue-2, or dengue-4) with arginine.