| 摘要 |
The present disclosure provides influenza hemagglutinin stem domain polypeptides comprising (a) an influenza hemagglutinin HA1 domain that comprises an HA1 N-terminal stem segment, covalently linked by a linking sequence of 0-50 amino acid residues to an HA1 C-terminal stem segment, and (b) an influenza hemagglutinin HA2 domain, wherein on or more amino acids in the HA2 domain have been mutated. Also provided are nucleic acids encoding the polypeptides, compositions comprising the polypeptides and/or nucleic acid molecules, as well as methods of their use, in particular in the detection, prevention and/or treatment of influenza. |
| 主权项 |
1. A polypeptide comprising:
(a) an influenza hemagglutinin HA1 domain that comprises an HA1 N-terminal stem segment comprising amino acids 1 to 52 of HA1, covalently linked by a linking sequence of 0 to 10 amino acid residues to an HA1 C-terminal stem segment comprising amino acids 321 to the end of HA1, wherein amino acids 53 to 320 are deleted, and (b) an influenza hemagglutinin HA2 domain, wherein the C-terminal amino acid residue of the HA1 C-terminal segment is any amino acid other than arginine (R) or lysine (K), wherein one or more amino acids at position 406, 409, 413 and 416 are mutated into an amino acid selected from the group consisting of S, T, N, Q, R, H, K, D, E and G, and wherein the polypeptides comprise a disulphide bridge between the amino acids at position 324 and 436, wherein the HA1 domain and HA2 domain are derived from an influenza A virus H1 subtype, and wherein the numbering is based on the numbering of amino acids of the H1N1 influenza strain A/Brisbane/59/2007 (SEQ ID NO: 1). |
