Influenza hemagglutinin and neuraminidase variants
Polypeptides, polynucleotides, methods, compositions, and vaccines comprising influenza hemagglutinin and neuraminidase variants are provided.
1. A reassortant influenza A virus comprising six internal genome segments from one or more donor viruses and a surface antigen genome segment encoding a hemagglutinin (HA) polypeptide comprising the amino acid sequence of SEQ ID NO: 45, wherein the six internal genome segments and the HA encoding genome segment are from different influenza A viruses.
2. The reassortant influenza A virus of claim 1 , further comprising a surface antigen genome segment encoding a neuraminidase (NA) polypeptide comprising the amino acid sequence of SEQ ID NO:46.
3. The reassortant influenza A virus of claim 1 , wherein the surface antigen genome segment encoding the HA polypeptide comprises the polynucleotide of SEQ ID NO:11.
4. The reassortant influenza A virus of claim 2 , wherein the surface antigen genome segment encoding the NA polypeptide comprises the polynucleotide of SEQ ID NO:12.
5. The reassortant influenza A virus of claim 1 , wherein the one or more donor viruses have one or more phenotypes selected from the group consisting of temperature-sensitive, cold-adapted, and attenuated.
6. The reassortant influenza A virus of claim 5 , wherein one or more donor viruses are selected from the group consisting of A/Ann Arbor/6/60 and A/Puerto Rico/8/34.
7. The reassortant influenza A virus of claim 1 , wherein the virus is killed or inactivated.
8. An immunogenic composition comprising an immunologically effective amount of the reassortant influenza A virus of claim 1 .
9. The immunogenic composition of claim 8 , wherein the reassortant influenza A virus is a 6:2 reassortant virus.
10. The immunogenic composition of claim 9 , wherein the one or more donor viruses have one or more phenotypes selected from the group consisting of temperature-sensitive, cold-adapted, and attenuated.
11. The immunogenic composition of claim 10 , wherein the one or more donor viruses are selected from the group consisting of A/Ann Arbor/6/60 and A/Puerto Rico/8/34.
12. A live attenuated influenza A H3 vaccine comprising the immunogenic composition of claim 8 .
13. A method of inducing an immune response against an influenza A viral infection in a subject, the method comprising: administering to the subject the reassortant influenza A virus of claim 1 in an amount effective to produce an immune response against the viral infection.
14. A reassortant influenza A virus produced according to a 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 one or more donor viruses; and at least one surface antigen genome segment encoding an HA polypeptide comprising the amino acid sequence of SEQ ID NO:45, wherein the six internal genome segments and the HA encoding genome segment are from different influenza A viruses;
ii) culturing the population of host cells; and
iii) recovering reassortant influenza A virus, wherein the reassortant influenza virus recovered is suitable for administration in an intranasal vaccine formulation.
15. The method of claim 14 , wherein the plurality of vectors further comprises a surface antigen genome segment encoding a NA polypeptide comprising the amino acid sequence of SEQ ID NO:46.
16. The method of claim 14 , wherein the surface antigen genome segment encoding the HA polypeptide comprises the polynucleotide of SEQ ID NO:11.
17. The method of claim 15 , wherein the surface antigen genome segment encoding the NA polypeptide comprises the polynucleotide of SEQ ID NO:12.
18. The method of claim 14 , wherein the one or more donor viruses have one or more phenotypes chosen from temperature-sensitive, cold-adapted, and attenuated.
19. The method of claim 14 , wherein the plurality of vectors consists of eight vectors.