Computationally optimized broadly reactive antigens for H1N1 influenza

摘要

The generation of optimized H1N1 influenza HA polypeptides for eliciting a broadly reactive immune response to H1N1 influenza virus isolates is described. The optimized HA polypeptides were developed through a series of HA protein alignments, and subsequent generation of consensus sequences, based on selected H1N1 viruses isolated from 1918-2012. Optimized H1N1 HA polypeptides, and compositions, fusion proteins and VLPs comprising the HA polypeptides are described. Condon-optimized nucleic acid sequences encoding the HA polypeptides are also described. Methods of eliciting an immune response against influenza virus in a subject are also described.

主权项

1. A recombinant influenza hemagglutinin (HA) polypeptide, comprising:
(i) the amino acid sequence of SEQ ID NO: 1 or the amino acid sequence of residues 2-566 of SEQ ID NO: 1; (ii) the amino acid sequence of SEQ ID NO: 2 with no more than 2 amino acid substitutions relative to SEQ ID NO: 2 or the amino acid sequence of residues 2-566 of SEQ ID NO: 2; (iii) the amino acid sequence of SEQ ID NO: 3 or the amino acid sequence of residues 2-566 of SEQ ID NO: 3; (iv) the amino acid sequence of SEQ ID NO: 5 or the amino acid sequence of residues 2-566 of SEQ ID NO: 5; (v) the amino acid sequence of SEQ ID NO: 6 with no more than 4 amino acid substitutions relative to SEQ ID NO: 6 or the amino acid sequence of residues 2-565 of SEQ ID NO: 6; or (vi) the amino acid sequence of SEQ ID NO: 7 or the amino acid sequence of residues 2-566 of SEQ ID NO: 7.