Influenza hemagglutinin and neuraminidase variants
Polypeptides, polynucleotides, methods, compositions, and vaccines comprising (avian pandemic) influenza hemagglutinin and neuraminidase variants are provided.
1. A reassortant influenza virus, wherein said virus comprises at least 6 internal genome segments from A/Ann Arbor/6/60 and at least one genome segment comprising a nucleic acid encoding a hemagglutinin polypeptide comprising the amino acid sequence of SEQ ID NO:15; wherein said nucleic acid comprises the nucleotide sequence of SEQ ID NO:5.
2. An immunogenic composition comprising an immunologically effective amount of the reassortant influenza virus of claim 1 .
3. A method for stimulating the immune system of an individual to produce a protective immune response against influenza virus, the method comprising administering to the individual an immunologically effective amount of the reassortant influenza virus of claim 1 in a physiologically effective carrier.
4. A method of prophylactic or therapeutic treatment of a viral infection in a subject, the method comprising: administering to the subject, the virus of claim 1 in an amount effective to produce an immunogenic response against the viral infection.
5. The method of claim 4 , wherein the subject is a human.
6. The immunogenic composition of claim 2 , wherein said reassortant influenza virus further comprises a neuramidinase genome segment comprising a nucleic acid encoding a neuramidinase polypeptide selected from the group consisting of: the polypeptides of SEQ ID NOs: 12, 14, 16, 18, and 20.
7. A live attenuated influenza vaccine comprising the composition of claim 2 .
8. A split virus or killed virus vaccine comprising the composition of claim 2 .
9. A live attenuated influenza vaccine comprising the composition of claim 6 .
10. A split virus or killed virus vaccine comprising the composition of claim 6 .
11. A method for producing influenza viruses in cell culture, the method comprising:
i) introducing into a population of host cells a plurality of vectors comprising nucleic acid sequences corresponding to at least 6 internal genome segments of the influenza strain A/Ann Arbor/6/60; and at least one genome segment comprising a nucleic acid encoding a hemagglutinin polypeptide comprising the amino acid sequence of SEO ID NO:15; wherein said nucleic acid comprises the nucleotide sequence of SEO ID NO:5,
ii) culturing the population of host cells at a temperature less than or equal to 35° C.; and,
iii) recovering a plurality of influenza viruses.
12. The immunogenic composition of claim 6 , wherein said neuramidinase polypeptide comprises the amino acid sequence of SEQ ID NO:16.
13. The immunogenic composition of claim 12 , wherein said neuramidinase polypeptide comprising the amino acid sequence of SEQ ID NO:16 is encoded by a nucleic acid comprising the nucleotide sequence of SEQ ID NO:6.
14. The method of claim 11 , wherein said plurality of vectors further comprise a nucleic acid sequence corresponding to a neuramidinase genome segment encoding a neuramidinase polypeptide selected from the group consisting of: SEQ ID NO:12, 14, 16, and 18.
15. The method of claim 14 , wherein said neuramidinase polypeptide comprises the amino acid sequence of SEQ ID NO:16.
16. The method of claim 15 , wherein said neuramidinase polypeptide comprising the amino acid sequence of SEQ ID NO:16 is encoded by a nucleic acid comprising the nucleotide sequence of SEQ ID NO:6.