INFLUENZA VIRUS VACCINES AND USES THEREOF

摘要

The present invention provides influenza hemagglutinin stem domain polypeptides comprising (a) an influenza hemagglutinin HA1 domain that comprises an HAl N-terminal stem segment, comprising the amino acids from position 1 to position x, preferably from position p to position x, of the HA1 domain, covalently linked by a linking sequence of 0-50 amino acid residues to an HA1 C- terminal stem segment, comprising the amino acids from position y to and including the C-terminal amino acid of the HA1 domain and (b) an influenza hemagglutinin HA2 domain, wherein the hemagglutinin stem domain polypeptide is resistant to protease cleavage at the junction between HA1 and HA2, and wherein one or more amino of the amino acids at positions 337, 340, 352, 353, 402, 406, 409, 413 and/or 416 have been mutated as compared to the corresponding positions in wild-type influenza HA.