A polypeptide comprising a Shiga toxin effector region, wherein: (i) the Shiga toxin effector region has at least 95% amino acid sequence identity to a wild-type Shiga toxin A Subunit amino acid sequence selected from: amino acid residues 75 to 251 of SEQ ID NO:1, amino acid residues 1 to 241 of SEQ ID NO:1, amino acid residues 1 to 251 of SEQ ID NO:1, and amino acid residues 1 to 261 of SEQ ID NO:1; and wherein, as compared to said wild-type Shiga toxin A Subunit amino acid sequence, the Shiga toxin effector region comprises a substitution of at least one amino acid residue in at least three epitope regions of the Shiga toxin A Subunit amino acid sequence selected from the group consisting of: 1-15 of SEQ ID NO:1; 27-37 of SEQ ID NO:1; 39-48 of SEQ ID NO:1; 53-66 of SEQ ID NO:1; 94-115 of SEQ ID NO:1; 141-153 of SEQ ID NO:1; 179-190 of SEQ ID NO:1; 205 of SEQ ID NO:1; 243-257 of SEQ ID NO:1; and 254-268 of SEQ ID NO:1; wherein, as compared to said wild-type Shiga toxin A Subunit amino acid sequence, the Shiga toxin effector region comprises the amino acid substitutions: S33I, G110A, and G147A; S45I, G110A, and G147A; D58A, G110A, and G147A; E60I, G110A, and G147A; D58A, G110A, G147A, and S186A; D58A, G110A, G147A, and G187A; D58A, G110A, G147A, and R188A; D58A, G110A, G147A, and S189A; S45I, D58A, E60I, G110A, and G147A; D58A, G110A, G147A, S186A, and R188A; D58A, G110A, G147A, G187A, and R188A; S33I, S45I, D58A, G110A, and G147A; S45I, G110A, G147A, D183A, D184A, and R188A; S45I, D58A, E60I, G110A, G147A, D183A, D184A, and R188A; or S45I, D58A, E60I, G62A, G110A, G147A, D183A, D184A, and R188A. wherein the Shiga toxin effector region has reduced antigenicity and/or immunogenicity as compared to said wild-type Shiga toxin A Subunit amino acid sequence; and wherein the Shiga toxin effector region is capable of exhibiting a Shiga toxin effector function selected from cellular internalization, subcellular routing, catalytic activity, and cytotoxicity. (i) the Shiga toxin effector region has at least 95% amino acid sequence identity to a wild-type Shiga toxin A Subunit amino acid sequence selected from: amino acid residues 75 to 251 of SEQ ID NO:1, amino acid residues 1 to 241 of SEQ ID NO:1, amino acid residues 1 to 251 of SEQ ID NO:1, and amino acid residues 1 to 261 of SEQ ID NO:1; amino acid residues 75 to 251 of SEQ ID NO:1, amino acid residues 1 to 241 of SEQ ID NO:1, amino acid residues 1 to 251 of SEQ ID NO:1, and amino acid residues 1 to 261 of SEQ ID NO:1; S33I, G110A, and G147A; S45I, G110A, and G147A; D58A, G110A, and G147A; E60I, G110A, and G147A; D58A, G110A, G147A, and S186A; D58A, G110A, G147A, and G187A; D58A, G110A, G147A, and R188A; D58A, G110A, G147A, and S189A; S45I, D58A, E60I, G110A, and G147A; D58A, G110A, G147A, S186A, and R188A; D58A, G110A, G147A, G187A, and R188A; S33I, S45I, D58A, G110A, and G147A; S45I, G110A, G147A, D183A, D184A, and R188A; S45I, D58A, E60I, G110A, G147A, D183A, D184A, and R188A; or S45I, D58A, E60I, G62A, G110A, G147A, D183A, D184A, and R188A. wherein the Shiga toxin effector region has reduced antigenicity and/or immunogenicity as compared to said wild-type Shiga toxin A Subunit amino acid sequence; and wherein the Shiga toxin effector region is capable of exhibiting a Shiga toxin effector function selected from cellular internalization, subcellular routing, catalytic activity, and cytotoxicity.