The present invention provides compositions useful for treating or preventing influenza infections. The composition comprises an isolated polypeptide including a sequence of at least 8 contiguous amino acid residues of the fusion initiation region (FIR) of an influenza hemagglutinin 2 protein or a peptide analog of the sequence. The FIR is a segment of the full length hemagglutinin 2 protein which is bounded by an amino-terminal region within the amino-terminal alpha-helix thereof and a carboxy terminus within the carboxy-terminal alpha-helix thereof, with a cysteine loop therebetween. The amino-terminal region of the FIR comprises a portion of the final 10 to 20 amino acid residues of the amino-terminal alpha-helix of the hemagglutinin 2 protein, and includes 3 or 4 hydrophobic amino acid residues, a positively-charged amino acid residue, a negatively-charged amino acid residue, and an aromatic amino acid residue. The carboxy terminus of the FIR is the carboxy terminus of the first peptide sequence of the hemagglutinin 2 protein beyond the amino terminal helix, which exhibits a positive Wimley-White interfacial hydrophobicity.
