Hemagglutinin modifications for improved influenza vaccine production
AssigneeSt. Jude Children's Research Hospital
InventorsNatalie Lee, Sanja Trifkovic, Rhodri Harfoot
Life of this patent
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Abstract
Mutation of adenosine methylation sites in nucleic acids encoding influenza virus hemagglutinin are provided that result in increases in vRNA, mRNA, and protein expression over time and increases in infectious titers when produced in mammalian cells.
Claims13
A modified nucleic acid molecule encoding influenza virus hemagglutinin comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO:1, wherein said nucleic acid molecule comprises an A->T mutation in the first position of codon 436 and optionally a C->T mutation in the third position of codon 433 with reference to the codons encoding the amino acid sequence of SEQ ID NO:
- 1.
A modified influenza virus hemagglutinin protein comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO:1 and a Thr436Ser amino acid substitution with reference to the amino acid sequence of SEQ ID NO:1.
A method for the production of influenza virus, comprising
- (a) transfecting host cells with a modified nucleic acid molecule encoding influenza virus hemagglutinin comprising an amino acid sequence having at least 80% sequence identity to SEQ ID NO:1, wherein said nucleic acid molecule comprises
- an A->T mutation in the first position of codon 436
- and optionally a C->T mutation in the third position of codon 433 with reference to the codons encoding the amino acid sequence of SEQ ID NO:1,
- (b) incubating the host cells under conditions that allow for influenza virus to be produced, and
- (c) isolating the influenza virus from the host cells.
Dependencies are inferred from the claim text.