A polypeptide isolated from S. pyogenes is described, having IgG cysteine protease activity. The protease is designated IdeS, Immunoglobulin G-degrading enzyme of S. pyogenes. A polypeptide comprises SEQ ID NO: 1 and variants and fragments thereof having IgG cysteine protease activity or the ability to generate an immune response against S. pyogenes in an individual. Polynucleotides encoding these polypeptides and the polypeptides may be used in generating an immune response in an individual. IdeS protease inhibitors may be used in the treatment of S. pyogenes infection.
