The invention refers to a cross-neutralizing antibody comprising at least one polyspecific binding site that binds to alpha-toxin (Hla) and at least one of the bi-component toxins of Staphylococcus aureus, which antibody comprises at least three complementarity determining regions (CDR1 to CDR3) of the antibody heavy chain variable region (VH), wherein A) the antibody comprises a) a CDR1 comprising or consisting of the amino acid sequence YSISSGMGWG (SEQ ID 1)； and b) a CDR2 comprising or consisting of the amino acid sequence SIDQRGSTYYNPSLKS (SEQ ID 2)； and c) a CDR3 comprising or consisting of the amino acid sequence ARDAGHGVDMDV (SEQ ID 3)； or B) the antibody comprises at least one functionally active CDR variant of a) the parent CDR1 consisting of the amino acid sequence of SEQ ID 1； or b) the parent CDR2 consisting of the amino acid sequence of SEQ ID 2； or c) the parent CDR3 consisting of the amino acid sequence of SEQ ID 3； wherein the functionally active CDR variant comprises at least one point mutation in the parent CDR sequence, and comprises or consists of the amino acid sequence that has at least 60% sequence identity with the parent CDR sequence. It further refers to such cross-neutralizing antibody which is a functionally active variant antibody of a parent antibody that comprises a polyspecific binding site of the VH amino acid sequence of SEQ ID 20, and the VL amino acid sequence of SEQ ID 39, which functionally active variant antibody comprises at least one point mutation in any of the framework regions (FR) or constant domains, or complementarity determining regions (CDR1 to CDR6) in any of SEQ ID 20 or SEQ 39, and has an affinity to bind each of the toxins with a Kd of less than 10−8M, preferably less than 10−9M.
