Computationally optimized broadly reactive antigens for H1N1 influenza

摘要

Described herein is the generation of optimized H1N1 influenza HA polypeptides for eliciting a broadly reactive immune response to H1N1 influenza virus isolates. 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 1918-2011. Provided herein are optimized H1N1 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 99% identical to SEQ ID NO: 1, wherein the amino acid sequence of the polypeptide comprises no more than 5 amino acid substitutions relative to SEQ ID NO: 1; (ii) the amino acid sequence of SEQ ID NO: 2; (iii) an amino acid sequence at least 99% identical to SEQ ID NO: 3, wherein the amino acid sequence of the polypeptide comprises no more than 6 amino acid substitutions relative to SEQ ID NO: 3; (iv) an amino acid sequence at least 99% identical to SEQ ID NO: 4, wherein the amino acid sequence of the polypeptide comprises no more than 8 amino acid substitutions relative to SEQ ID NO: 4; (v) an amino acid sequence at least 98% identical to SEQ ID NO: 5, wherein the amino acid sequence of the polypeptide comprises no more than 10 amino acid substitutions relative to SEQ ID NO: 5; (vi) an amino acid sequence at least 99% identical to SEQ ID NO: 6, wherein the amino acid sequence of the polypeptide comprises no more than 8 amino acid substitutions relative to SEQ ID NO: 6; (vii) an amino acid sequence at least 97% identical to SEQ ID NO: 7, wherein the amino acid sequence of the polypeptide comprises no more than 10 amino acid substitutions relative to SEQ ID NO: 7; (viii) an amino acid sequence at least 99% identical to SEQ ID NO: 8, wherein the amino acid sequence of the polypeptide comprises no more than 10 amino acid substitutions relative to SEQ ID NO: 8; (ix) the amino acid sequence of SEQ ID NO: 9; (x) an amino acid sequence at least 99% identical to SEQ ID NO: 10, wherein the amino acid sequence of the polypeptide comprises no more than 8 amino acid substitutions relative to SEQ ID NO: 10; or (xi) an amino acid sequence at least 99% identical to SEQ ID NO: 11, wherein the amino acid sequence of the polypeptide comprises no more than 5 amino acid substitutions relative to SEQ ID NO: 11.