Computationally optimized broadly reactive antigens for H3N2, H2N2, and B influenza viruses

摘要

Described herein is the generation of optimized H3N2, H2N2 and B influenza HA polypeptides for eliciting a broadly reactive immune response to influenza virus isolates. The optimized HA polypeptides were developed through a series of HA protein alignments, and subsequent generation of consensus sequences, based on H3N2, H2N2 and B influenza isolates. Provided herein are optimized H3N2, H2N2 and B influenza HA polypeptides, and compositions, fusion proteins and VLPs comprising the HA polypeptides. Further provided are codon-optimized nucleic acid sequences encoding the HA polypeptides. Methods of eliciting an immune response against influenza virus in a subject are also provided by the present disclosure.

主权项

1. A recombinant influenza hemagglutinin (HA) polypeptide, comprising:
(i) an amino acid sequence at least 97.7% identical to residues 2-566 of SEQ ID NO: 8; (ii) an amino acid sequence at least 99.6% identical to residues 2-562 of SEQ ID NO: 1; (iii) an amino acid sequence at least 99.4% identical to residues 2-562 of SEQ ID NO: 2; (iv) an amino acid sequence comprising residues 2-562 of SEQ ID NO: 3; (v) an amino acid sequence at least 99.7% identical to residues 2-562 of SEQ ID NO: 4; (vi) an amino acid sequence at least 99.6% identical to residues 2-584 of SEQ ID NO: 5; (vii) an amino acid sequence at least 98.8% identical to residues 2-585 of SEQ ID NO: 6; (viii) an amino acid sequence comprising residues 2-585 of SEQ ID NO: 7; (ix) an amino acid sequence at least 98.4% identical to residues 2-566 of SEQ ID NO: 9; (x) an amino acid sequence at least 97.8% identical to residues 2-566 of SEQ ID NO: 10; or (xi) an amino acid sequence at least 98.9% identical to residues 2-566 of SEQ ID NO: 11.