Influenza hemagglutinin and neuraminidase variants
Polypeptides, polynucleotides, methods, compositions, and vaccines comprising influenza hemagglutinin and neuraminidase variants are provided.
1. A reassortant influenza virus comprising a polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 37.
2. The virus of claim 1 , wherein the virus comprises 6 internal genome segments from one or more donor viruses.
3. The virus of claim 2 , wherein one donor virus is A/Ann Arbor/6/60, or A/Puerto Rico/8/34.
4. An immunogenic composition comprising an immunologically effective amount of the recombinant influenza virus of claim 2 .
5. The virus of claim 2 , wherein the 6 internal genome segments of the one or more donor viruses are selected for comprising one or more phenotypic attributes selected from the group consisting of: attenuated, cold adapted and temperature sensitive.
6. The virus of claim 1 , wherein the virus is killed or inactivated.
7. An immunogenic composition comprising the reassortant virus of claim 1 .
8. The composition of claim 7 wherein the reassortant virus is a 6:2 reassortant virus comprising 6 internal genome segments from one or more donor viruses.
9. The composition of claim 8 , wherein the 6 internal genome segments of the one donor virus are selected for comprising one or more phenotypic attributes selected from the group consisting of: attenuated, cold adapted and temperature sensitive.
10. The composition of claim 9 , wherein one donor virus is A/Ann Arbor/6/60, or A/Puerto Rico/8/34.
11. A live attenuated influenza vaccine comprising the composition of claim 7 .
12. The composition of claim 7 , further comprising one or more pharmaceutically acceptable excipients.
13. The virus of claim 1 , wherein the virus further comprises a polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 38.
14. A method for producing the reassortant influenza virus of claim 1 in cell culture, the method comprising:
i) introducing a plurality of vectors into a population of host cells capable of supporting replication of influenza viruses, which plurality of vectors comprises nucleotide sequences corresponding to at least 6 internal genome segments of a first influenza strain; and one genome segment encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 37;
ii) culturing the population of host cells; and
iii) recovering the influenza virus.
15. The method of claim 14 , wherein the at least 6 internal genome segments of the first influenza virus strain are selected for comprising one or more phenotypic attributes selected from the group consisting of: attenuated, cold adapted and temperature sensitive.
16. The method of claim 14 , wherein the first influenza strain is an influenza A strain.
17. The method of claim 14 , wherein the first influenza strain is A/Ann Arbor/6/60, or A/Puerto Rico/8/34.
18. The method of claim 14 , wherein the plurality of vectors is a plurality of plasmid vectors.
19. The method of claim 14 , wherein the population of host cells comprises one or more of: Vero cells, PerC6 cells, MDCK cells, 293T cells, or COS cells.
20. The method of claim 14 , wherein the method does not comprise use of a helper virus.
21. The method of claim 14 , wherein the plurality of vectors consists of eight vectors.
22. An influenza virus produced by the method of claim 14 , wherein the influenza virus is suitable for administration in an intranasal vaccine formulation.
23. A method of prophylactic or therapeutic treatment of an influenza A H3 viral infection in a subject, the method comprising: administering to the subject the virus of claim 5 in an amount effective to produce an immunogenic response against the influenza A H3 infection.
24. A method of prophylactic or therapeutic treatment of an influenza A H3 viral infection in a subject, the method comprising: administering to the subject the virus of claim 6 in an amount effective to produce an immunogenic response against the influenza A H3 viral infection.