In our earlier studies, we constructed a hybrid strain of Shigella dysenteriae type 1 by introducing a plasmid vector pPR 1347. After introduction of a lipopolysaccharide (LPS) biosynthesis gene, virulent Shigella dysenteriae type 1 strain became avirulent. In our present study, we have evaluated the immune response and protective efficacy of avirulent live transconjugant Shigella hybrid (LTSH) strain against wild type Shigella dysenteriae type 1, after four doses of oral (rabbit) and intranasal (mouse) immunizations. Serum IgG titers showed exponential increase during immunization and peaking on the 28th day and remained at that level till the 35th day in both the rabbit and the mouse models. When tested, serum IgG titers persisted for 63 days in mice and relatively high for 150 days in case of rabbits. Protection studies showed 100% protection against the challenge with wild type Shigella dysenteriae type 1 strain in rabbits and 80% protection in mice. Our results suggested that the LTSH strain could be a useful vaccine candidate strain in the future.