An auxotrophic live oral Shigella flexneri vaccine: development and testing

Through transduction, a wild-type strain of Shigella flexneri serotype Y (SFL1) was rendered auxotrophic and dependent on aromatic metabolites that are not available in mammalian tissues. Monkeys that were orally vaccinated with 10(11) bacteria of the transductant strain SFL114 remained healthy when challenged with 10(11) bacteria of wild-type strains of S. flexneri serotypes Y, 1b, and 2a. The safety and immunogenicity of SFL114 were next studied in volunteers who were given either 10(9) or 10(10) SFL114 bacteria orally. Mild intestinal discomfort that lasted for 1-2 days was reported by three (12%) of 25 volunteers given 10(9) live SFL114 bacteria and by 13 (54%) of 24 volunteers given 10(10) live SFL114 bacteria. A local intestinal secretory IgA response to the S. flexneri O-antigen was recorded. The in vitro and in vivo results suggest that the aroD transductant SFL114 possesses properties that are desirable in an oral live candidate vaccine.