West nile virus vaccine
The invention provides chimeric flavivirus vaccines against West Nile virus and methods of using these vaccines to prevent or treat West Nile virus infection.
1. A chimeric flavivirus comprising nucleic acid sequences encoding the pre-membrane and envelope proteins of a West Nile virus, and nucleic acid sequences encoding capsid and non-structural proteins of a yellow fever virus, wherein the envelope protein of the chimeric flavivirus comprises a substitution of alanine at position 316 with valine, and a substitution of lysine at position 440 with arginine.
2. The chimeric flavivirus of claim 1 , further comprising an amino acid substitution in position 107 of the envelope protein of the chimeric flavivirus.
3. The chimeric flavivirus of claim 2 , wherein the amino acid substitution at position 107 of the envelope protein of the chimeric flavivirus is leucine to phenylalanine, or a conservative amino acid of phenylalanine.
4. The chimeric flavivirus of claim 3 , wherein the amino acid substitution at position 107 of the envelope protein of the chimeric flavivirus is leucine to phenylalanine.
5. The chimeric flavivirus of claim 1 , wherein the West Nile virus is strain NY99-flamingo 382-99.
6. The chimeric flavivirus of claim 1 , wherein the yellow fever virus is strain YF 17D.
7. The chimeric flavivirus of claim 1 , further comprising a substitution in one or more amino acid position selected from 138, 176, and 280 of the envelope protein of the chimeric flavivirus.
8. A method of inducing an immune response to West Nile virus in a subject, the method comprising the chimeric flavivirus of claim 1 to the subject.
9. The method of claim 8 , wherein the chimeric flavivirus further comprises an amino acid substitution in position 107 of the envelope protein.
10. The method of claim 9 , wherein the amino acid substitution at position 107 of the envelope protein is leucine to phenylalanine, or a conservative amino acid of phenylalanine.
11. The method of claim 10 , wherein the amino acid substitution at position 107 of the envelope protein is leucine to phenylalanine.
12. The method claim 8 , wherein the subject is at risk of developing, but does not have, West Nile virus infection.
13. The method of claim 8 , wherein the subject is infected with West Nile virus.
14. The method of claim 8 , wherein the chimeric flavivirus is administered to the subject a single time.
15. The method of claim 14 , further comprising a follow-up immunization.
16. The method of claim 8 , further comprising administration of an adjuvant to the subject.
17. A nucleic acid molecule encoding the chimeric flavivirus of claim 1 , or the complement thereof.
18. A method of making a chimeric flavivirus, the method comprising introducing the nucleic acid molecule of claim 17 into cells.