Enterohemorrhagic Escherichia coli O157∶H7 (EHEC O 157∶H7) causes hemorrhagic colitis and form characteristic attaching and effacing (A/E) lesions.Due to the severe sequelae of EHEC O157∶H7, it is critical to develop effective vaccines.We developed a candidate vaccine by inserting the bivalent antigen espA-Tir-M composed of espA and the Tir central domain into Lactobacillus acidophilus.The recombinant L.acidophilus (LA-ET) was safe in cell model and excluded EHEC O157∶H7 from LoVo cells by nearly 94% and 60% in exclusion and competition assays, respectively.Meanwhile, LA-ET inhibits EHEC O157∶H7 to induce attaching and effacing (A/E) lesions in vitro.Oral immunization LA-ET also enhanced interferon-γ and interleukin-4 and-10 production, which was associated with mixed helper T (Th)1/Th2 cell responses, and protected against EHEC O157∶H7 colonization and infection in mice at a rate of 80%.A histopathological analysis revealed that orally administered LA-ET reduce or inhibit the A/E lesions and toxin-induced systemic injury.These findings demonstrate that LA-ET induces both humoral and cellular immune responses in mice and is therefore a promising vaccine against EHEC O157∶H7 infection.