In humans and most animal species such as pigs, vaccination via the oral route is a prerequisite for induction of a protective immunity against enteropathogens. Hereto, live attenuated microorganisms can be used. However, these microorganisms often are either too attenuated to induce sufficient intestinal immunity or are still too virulent resulting in clinical signs. We previously demonstrated that it is possible to induce immunity against enteropathogens by targeting antigen towards enterocytes. Maltose-binding protein (MBP) is part of the maltose/maltodextrin system of Escherichia coli. MBP is a relatively small protein (42.5 kDa) approximately 3 × 4 × 6.5 nm in size with surface residues capable of both hydrogen bonding interactions and hydrophobic interactions. Recombinant proteins are often fused to MPB to improve their yield and to increase their solubility. In mice, these fusion proteins showed an enhanced immunogenicity following systemic immunization. More recently, this has been attributed to interaction of MBP with TLR4 on dendritic cells (DCs). TLR4 is also expressed in the enterocytes of the gut. Therefore, we examined if oral administration of MPB-FedF to 4-week-old pigs could be used to induce an immune response against F18+ verotoxigenic E. coli in pigs. Also we examined if the oral administration of MBP to pigs is able to induce an immune response. In both experiments cholera toxin was used as oral adjuvant