Abstract: The present invention provides a method of increasing the recombinant expression and solubility of influenza A virus M2 polypeptide comprising nucleic acids encoding variants of the M2 protein of influenza A virus in which transmembrane and other hydrophobic domains have been deleted. The present invention also provides purified polypeptides encoded by the nucleic acids, which polypeptides are immunogenic and are less hydrophobic than full-length M2. Also provided are vaccines comprising variants of M2 expressed in prokaryotic hosts. Further provided are methods of preventing influenza A infection using vaccines comprised of variants of M2. Also provided are antibodies raised against the variants of M2, and use of such antibodies in diagnosis and treatment of influenza A infections.