Prevention of Shigellosis by a Salmonella typhi-Shigella sonnei Bivalent Vaccine

Abstract

We genetically modified attenuated Salmonella typhi strain Ty21a to express the form IO polysaccharide antigen of Shigella sonnet. Three doses of this bivalent, live oral vaccine strain (1–8 × 10⁹ organisms/dose) were given to young adults who, along with unvaccinated controls, were challenged one month later with pathogenic S. sonnei. The vaccinees had 40% protection against diarrhea and 56% against Hematest®-positive diarrhea. Two of three vaccine lots provided higher levels of protection (53% against diarrhea and 71% against Hematest-positive diarrhea), but the third lot, prepared for a large-scale field trial, demonstrated no protective efficacy. Vaccinees had serum and local intestinal immune responses to S. sonnei lipopolysaccharide, and the presence of specific serum 19A or IgG antibody before challenge with pathogenic S. sonnei was correlated with protection from illness. Some lots of this bivalent vaccine strain provide significant protection against S. sonnei disease, but the problem of lot-to-Iot variability must be overcome.