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US 11,807,872 B2Granted
Recombinant influenza viruses with stabilized HA for replication in eggs
AssigneesWisconsin Alumni Research Foundation (WARF), The University of Tokyo
InventorsYoshihiro Kawaoka, Shinya Yamada, Shiho Chiba
Life of this patent
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Abstract
Modified influenza virus neuraminidases are described herein that improve viral replication, thus improving the yield of vaccine viruses. Expression of such modified neuraminidases by influenza virus may also stabilize co-expressed hemagglutinins so that the hemagglutinins do not undergo mutation or decrease the need for HA binding to cells.
Claims17
An isolated recombinant influenza virus comprising a selected neuraminidase (NA) viral segment encoding a plurality of selected residues in NA,
- wherein the selected NA viral segment encodes a NA having an isoleucine (I) at residue 148, and wherein the plurality of selected residues in the NA includes when the NA does not encode an aspartic acid (D) at position 151, does not encode an asparagine (N) at position 245, does not encode a threonine (T) at position 329, does not encode a lysine (K) at position 344, does not encode a glycine (G) at position 346, does not encode a histidine (H) at residue 347, or does not encode a threonine at position 369, or any combination thereof, wherein the numbering is based on N2, wherein the recombinant influenza virus has enhanced replication in avian eggs, has reduced sialidase activity, enhanced binding to a2-3 sialosides, or has a reduction in hemagglutinin (HA) mutations when grown in avian eggs relative to a corresponding influenza virus that has a NA that encodes a threonine or lysine at residue 148, encodes an aspartic acid at residue 151, encodes an asparagine at residue 245, encodes a threonine at residue 329, encodes a lysine at residue 344, encodes a glycine at residue 346, encodes a histidine at residue 347, and encodes a threonine at position 369, wherein the numbering is based on N2 of SEQ ID NO:53.
Dependencies are inferred from the claim text.