Immunogen structure and antigenicity can be characterized empirically and also computationally. Recent advance in computational modeling and structural biology allows to assess structure properties of immunogens and to accelerate vaccine development . In the current study, we cloned the CFA/I/II/IV MEFA gene without the 6xHis-tag, applied computational modelling to in silico characterize the antigenic structure of a tag-less CFA/I/II/IV MEFA, and examined immunogenicity of the new MEFA antigen in mouse immunization. In addition, we examined computational data and empirical data for immunogenicity congruence to assess potential application of computation simulation for structure-based ETEC vaccine development, likely proof of concept of MEFA application in structural vaccinology.