Abstract: Shigella vaccine strains whose primary attenuating feature is deletion of the virG(icsA) gene and additional two or more deletions in setAB(shET1), senA(shET2), senB(shET2-2), stxAB, and msbB2 genes. Thus, the vaccine strain will have three or more deletions in the identified genes, will be safer, and will reduce or eliminate symptoms of fever and diarrhea in humans. The following specific vaccine strains have been constructed: WRSS3 (?senA, ?senB, ?virG, ?msbB2), WRSf2G15 (?virG, ?setAB, ?senA, ?senB, ?msbB2), and WRSd5 (?virG, ?stxAB, ?senA, ?senB, ?msbB2).