Recombinant influenza antigens

By introducing specific amino acid mutations into the core of influenza HA polypeptides, the limitations of existing influenza vaccine production methods were solved, and stable and highly immunogenic recombinant influenza HA polypeptides were obtained, achieving efficient expression and purification in mammalian cells.

CN113597428BActive Publication Date: 2025-04-01JANSSEN VACCINES & PREVENTION BV
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Patent Information

Application Number
CN202080019855.2
Authority / Receiving Office
CN · China
Patent Type
Patents(China)
Current Assignee / Owner
Priority Date
2019-04-25
Filing Date
2020-04-23
Publication Date
2025-04-01
Estimated Expiration
2040-04-23

AI Technical Summary

Technical Problem

The existing influenza vaccine production methods rely on eggs, which have limitations such as changes in HA during production, egg allergies problems and unstable supply, making it difficult to effectively produce recombinant influenza HA polypeptides with high immunogenicity, stability and high yield.

Method used

By introducing specific amino acid mutations, such as the amino acid at position 355 is tryptophan (W), the amino acid at position 432 is isoleucine (I), and expressed in the core of the HA polypeptide, a stable recombinant influenza A hemagglutinin (HA) polypeptide, including the trimeric polypeptide form.

Benefits of technology

A stable recombinant influenza HA polypeptide is achieved at a high level of expression and purification in mammalian cells, with increased melting temperature and better stability, able to correctly fold and induce an immune response to HA.

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Abstract

The present invention provides recombinant influenza A hemagglutinin (HA) polypeptides, which comprise the HA1 and HA2 domains of influenza A virus HA and comprise an amino acid sequence in which: (a) the amino acid at position 355 is W; and (b) the amino acid at position 432 is I and / or the amino acid at position 380 is I; and wherein the numbering of the amino acid positions in the amino acid sequence of the HA polypeptide is according to the numbering of the amino acids in the amino acid sequence of HA, the HA being derived from an H3N2 influenza reference strain, particularly an H3N2A / Aichi / 2 / 68 reference strain (SEQ ID NO: 1); and provide immunogenic fragments thereof, nucleic acid molecules encoding the polypeptides or immunogenic fragments, and uses thereof.
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