Studies with aNew Generation of Oral Attenuated Shigella Vaccine: Escherichia coli Bearing Surface Antigens of

In an attempt to develop a safe, proliferating, oral, attenuated vaccine against shigel-losis, genes that control the synthesis of group- and type-specific somatic antigens of Shigella flexneri 2a were transferred via conjugation to a recipient strain of Escheri-chia coli. The resultant hybrid (E. coli expressing shigella surface antigens) vaccine strain, PGAI 42-1-15, believed to have a complete (smooth) lipopolysaccharide, was given to volunteers in two vaccination-challenge studies. The vaccine was well tol-erated and gave evidence of intestinal proliferation. In trial no. I, volunteers given two doses of vaccine one month apart were challenged after eight weeks with 104 viru-lent S. flexneri 2a. Attack rates were comparable in vaccinees (50%) and controls (40%). In trial no. 2, vaccinees were given three weekly doses of vaccine and were challenged four weeks later with a small inoculum (102) of S. flexneri 2a. Again, attack rates among vaccinees (47%) and controls (39%) were similar. It is unclear why this theoretically ideal, live shigella vaccine failed to protect against S. [lexneri 2a. Attenuated, single-step mutants of Shigella, such as streptomycin-dependent strains [1-3] and co