The recent rise of antibiotic resistance and lack of an effective vaccine make the scenario of shigellosis alarming in developing countries like Bangladesh. In recent years, our group reported the vaccine efficacy of a non-pathogenic Escherichia albertii strain DM104 in different animal models, where an ocularly administered vaccine in the guinea pig eye model against Shigella dysenteriae type 4 challenge showed high protective efficacy and also induced a high titer of serum IgG against S. dysenteriae type 4 whole cell lysate (WCL) and LPS. In this study, we report further evaluation of the non-invasive and non-toxic environmental strain DM104 as a vaccine candidate against S. dysenteriae type 4 in mice model. Oral immunization of live DM104 bacterial strain demonstrated better protective immunity in mice model by showing 90% protection in mice against live S. dysenteriae type 4 lethal dose challenge and by inducing effective humoral and mucosal immune responses.  Kulcsszavak: Shigella dysenteriae, Escherichia albertii, shigellosis, protective efficacy, vaccine