An isolated recombinant vaccinia virus complement control protein (hrVCP) polypeptide comprises a modified amino acid sequence comprising one or more amino acid substitutions to an amino acid sequence as set forth in SEQ ID NO: 2. The hrVCP polypeptide exhibits a complement activation regulatory activity greater than a complement activation regulatory activity of a polypeptide comprising the amino acid sequence as set forth in SEQ ID NO: 2. The one or more amino acid substitutions are selected from the group consisting of H98Y, E102K, E108K, E120K, and combinations thereof.