Abstract: The present disclosure relates to a polypeptide comprising hemagglutinin stem domain fragments that can elicit broadly cross-reactive anti-influenza antibodies and confer protection against influenza virus. The disclosure also provides a method of preparing the polypeptide with biochemical and biophysical properties that enhance its immunogenic properties. Also provided are recombinant DNA constructs, vectors, and host cells comprising the nucleic acid encoding the polypeptide, as well as uses of the polypeptide, particularly in the prevention, and detection of influenza.