Reassortant influenza B viruses
Polypeptides, polynucleotides, methods, compositions, and vaccines comprising influenza hemagglutinin and neuraminidase variants are provided.
1. A reassortant influenza B virus comprising a polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 67.
2. The reassortant influenza B virus of claim 1 , wherein the virus comprises 6 internal genome segments from one or more donor viruses.
3. The reassortant influenza B virus of claim 2 , wherein the donor virus is or B/Ann Arbor/1/66.
4. An immunogenic composition comprising an immunologically effective amount of the reassortant influenza B virus of claim 2 .
5. The reassortant influenza B virus of claim 2 , wherein the 6 internal genome segments of the one or more donor viruses are selected as conferring one or more phenotypic attributes selected from the group consisting of: attenuated, cold-adapted and temperature-sensitive.
6. A reassortant influenza B virus produced by 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 a first influenza B strain; and one genome segment encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 67;
ii) culturing the population of host cells; and
iii) recovering reassortant influenza B virus,
wherein the reassortant influenza B virus is suitable for administration in an intranasal vaccine formulation.
7. An immunogenic composition comprising the reassortant influenza B virus of claim 1 .
8. The composition of claim 7 , wherein the reassortant influenza B virus is a 6:2 reassortant influenza B virus comprising 6 internal genome segments from one or more influenza B donor viruses.
9. The composition of claim 8 , wherein the 6 internal genome segments of the one or more influenza B donor viruses are selected as conferring one or more phenotypic attributes selected from the group consisting of: attenuated, cold adapted and temperature sensitive.
10. The composition of claim 9 , wherein the donor virus is B/Ann Arbor/1/66.
11. The composition of claim 7 , further comprising one or more pharmaceutically acceptable excipients.
12. The reassortant influenza B virus of claim 1 , wherein the virus further comprises a polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 68.
13. The reassortant influenza B virus of claim 1 , wherein the virus is killed or inactivated.
14. An immunogenic vaccine composition comprising an immunologically effective amount of the reassortant influenza B virus of claim 9 .
15. An immunogenic vaccine composition comprising an immunologically effective amount of the reassortant influenza B virus of claim 13 .
16. A method for producing the reassortant influenza B 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 B strain; and one genome segment encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 67;
ii) culturing the population of host cells; and
iii) recovering the influenza B virus.
17. The method of claim 16 , wherein the at least 6 internal genome segments of the first influenza B virus strain are selected as conferring one or more phenotypic attributes selected from the group consisting of: attenuated, cold-adapted and temperature-sensitive.
18. The method of claim 16 , wherein the plurality of vectors consists of eight vectors.
19. A method of prophylactic or therapeutic treatment of an influenza B viral infection in a subject, the method comprising: administering to the subject the reassortant influenza B virus of claim 1 , in an amount effective to produce an immunogenic response against the influenza B viral infection.
20. A method of prophylactic or therapeutic treatment of an influenza B viral infection in a subject, the method comprising: administering to the subject the reassortant influenza B virus of claim 13 in an amount effective to produce an immunogenic response against the influenza B viral infection.
21. The method of claim 16 , wherein the influenza B virus further comprises a polynucleotide encoding a polypeptide comprising the amino acid sequence of SEQ ID NO: 68.