Influenza hemagglutinin and neuraminidase variants
Polypeptides, polynucleotides, methods, compositions, and vaccines comprising (avian pandemic) influenza hemagglutinin and neuraminidase variants are provided.
1. A 6:2 reassortant influenza virus, wherein said virus comprises 6 internal genome segments from one or more donor viruses and 2 surface antigen genome segments, wherein the surface antigen genome segments encode an HA and a NA polypeptide, wherein the surface antigen genome segment that encodes the HA polypeptide produces a polypeptide comprising the amino acid sequence of SEQ ID NO:41.
2. The 6:2 reassortant influenza virus of claim 1 , wherein the one or more donor viruses comprises one or more of the following phenotypes: temperature-sensitive, cold-adapted, or attenuated.
3. The 6:2 reassortant influenza virus of claim 1 , wherein the one or more donor viruses are PR8.
4. The 6:2 reassortant influenza virus of claim 1 , wherein the one or more donor viruses are A/Leningrad/17.
5. An immunogenic vaccine composition comprising an immunologically effective amount of the reassortant influenza virus of claim 1 .
6. An immunogenic vaccine composition comprising an immunologically effective amount of the reassortant influenza virus of claim 2 .
7. 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.
8. 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 2 in a physiologically effective carrier.
9. 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.
10. The method of claim 7 , wherein said virus is killed or inactivated.
11. The method of claim 9 , wherein said virus is killed or inactivated.
12. The method of claim 9 , wherein the subject is a human.
13. A live attenuated influenza vaccine comprising the composition of claim 5 .
14. A live attenuated influenza vaccine comprising the composition of claim 6 .
15. A method for producing an influenza virus in cell culture, the method comprising:
i) introducing into a population of host cells, which population of host cells is capable of supporting replication of influenza virus, a plurality of vectors comprising nucleotide sequences corresponding to:
(a) at least 6 internal genome segments of a first influenza strain, and, at least one genome segment encoding an HA surface antigen polypeptide wherein the surface antigen polypeptide comprises the amino acid sequence of SEQ ID NO: 41; or
(b) at least 6 internal genome segments of a first influenza strain and which influenza strain comprises one or more phenotypic attributes selected from the group consisting of: attenuated, cold adapted and temperature sensitive; and at least one genome segment encoding an HA surface antigen wherein the surface antigen polypeptide comprises the amino acid sequence of SEQ ID NO: 41,
ii) culturing the population of host cells at a temperature less than or equal to 35° C.; and,
iii) recovering an influenza virus.
16. An immunogenic composition comprising an immunologically effective amount of the influenza virus produced by the method of claim 15 .
17. 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 influenza virus produced by the method of claim 15 in a physiologically effective carrier.
18. 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 the immunogenic composition of claim 16 .
19. A live attenuated influenza vaccine comprising the immunogenic composition of claim 16 .
20. A split virus or killed virus vaccine comprising the immunogenic composition of claim 16 .
21. The 6:2 reassortant virus of claim 1 , wherein the one or more donor viruses are A/Ann Arbor/6/60.
22. The 6:2 reassortant virus of claim 1 , wherein the one or more donor viruses are other than A/Ann Arbor/6/60.