Safety and immunogenicity of WRSd1, a live attenuatedShigella dysenteriaetype 1 vaccine candidate

AmongShigellaserotypesShigella dysenteriaetype 1 produces the most severe disease, including cases of hemolytic-uremic syndrome and pandemic outbreaks. WRSd1 is a liveS. dysenteriae1 strain attenuated by deletion of thevirG(icsA) gene, which encodes a protein that mediates intercellular spread, andstxAandstxB, which encode the Shiga toxin. In this Phase I trial five groups of eight subjects ingested escalating doses of WRSd1 ranging from 103to 107CFU. No subject experienced fever or shigellosis, but 20% had diarrhea. Approximately two-thirds of subjects developed an IgA-ASC response to LPS. Days of fecal shedding of the vaccine strain, but not dose ingested, correlated with stronger immune responses. These results suggest that to be effective an attenuatedShigellavaccine must colonize well.