Recombinant influenza antigens
The invention provides recombinant influenza A hemagglutinin (HA) polypeptides, comprising an HA1 and a HA2 domain of an influenza A virus HA, and comprising an amino acid sequence wherein: (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 amino acids in the amino acid sequence of HA from a reference H3N2 influenza strain, in particular the reference strain H3N2 A/Aichi/2/68 (SEQ ID NO: 1), immunogenic fragments thereof, nucleic acid molecules encoding said polypeptides or immunogenic fragments, and uses thereof.
1 . A recombinant influenza A hemagglutinin (HA) polypeptide, comprising an HA1 and a HA2 domain of an influenza A virus HA, and comprising an amino acid sequence wherein:
(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 amino acids in the amino acid sequence of HA from a reference H3N2 influenza strain, in particular the reference strain H3N2 A/Aichi/2/68 (SEQ ID NO: 1).
2 . The HA polypeptide according to claim 1 , comprising an amino acid sequence wherein:
(a) the amino acid at position 388 is M; and/or
(b) the amino acid at position 478 is I.
3 . The HA polypeptide according to claim 1 , wherein the polypeptide does not comprise a protease cleavage site between the HA1 and HA2 domain.
4 . The HA polypeptide according to claim 1 , wherein the HA1 and HA2 domain are from a Group 1 and/or a Group 2 influenza A virus.
5 . The HA polypeptide according to claim 1 , comprising a truncated HA1 and/or HA2 domain.
6 . The HA polypeptide according to claim 5 , wherein the transmembrane and intracytoplasmic domains have been deleted from the HA2 domain.
7 . The HA polypeptide according to claim 5 , wherein at least the C-terminal part of the HA2 domain starting with the amino acid corresponding to the amino acid at position 515 has been deleted.
8 . The HA polypeptide according to claim 1 , comprising a detecting and/or purification tag positioned C-terminal of the HA2 domain.
9 . A multimeric polypeptide comprising at least two HA polypeptides according to claim 1 .
10 . A multimeric polypeptide according to claim 9 , wherein the polypeptide is trimeric and comprises three HA polypeptides according claim 1 .
11 . A method for producing a recombinant HA polypeptide according to claim 1 , comprising expressing a nucleic acid molecule encoding the HA polypeptide of claim 1 in a prokaryotic or eukaryotic cell, and isolating the HA polypeptide or fragment thereof from the cell.
12 . An immunogenic composition comprising an HA polypeptide according to claim 1 , and a pharmaceutically acceptable carrier.
13 . A composition for inducing an immune response against an influenza virus, comprising the HA polypeptide according to claim 1 .
14 . An influenza virus vaccine composition comprising the HA polypeptide according to claim 1 .