Congruence at overall immunogenicity of this tag-less CFA/I/II/IV MEFA between computational data and empirical mouse immunization data suggest the potential application of structural vaccinology in ETEC vaccine development. Whether antigen immunogenicity congruence also occurs from data in human immunization studies will be revealed in future human volunteer studies. It should be noted that some inconsistency between the ASA predicted from molecular dynamics simulation and the in vitro antibody protection among two individual epitopes warrants further improvement of structural vaccinology including the prediction of neutralizing epitopes instead of immunodominant epitopes; in return, it may also validate the need of empirical studies to confirm computational data.