Compositions and methods for stimulating an immune response against Shiga toxin-producing Escherichia coli (STEC) antigens are disclosed. The compositions include a multiple epitope fusion protein comprising more than one epitope of an immunogenic STEC protein from more than one STEC serotype. Additional compositions include at least two purified STEC proteins, wherein the STEC proteins are selected from a full-length STEC protein, an immunogenic fragment or variant thereof, wherein at least one of the STEC proteins generates antibodies that react with STEC O157 and at least one other STEC serotype.
