Abstract
Improved live oral typhoid fever vaccines may be engineered by deletion of Salmonella-specific virulence genes in Salmonella typhi. Ty445, an aroA-deleted S. typhi Ty2 strain also deleted for the phoP/phoQ Salmonella typhimurium virulence regulatory locus, was tested in human volunteers. Volunteers received escalating single dosed of the vaccine; subsequently 14 individuals received two doses of 10 10 c.f.u. without significant side-effects. Control vaccinees received four doses of the live oral typhoid vaccine Ty21a. Of controls, 5 8 seroconverted as measured by increases in serum IgG directed against S. typhi O antigen or whole bacterial antigens in ELISAs. Only 2 14 volunteers receiving the experimental vaccine Ty445 seroconverted. Although a ΔaroA ΔphoP/phoQ S. typhi strain is overattenuated for use as a typhoid fever vaccine, our data demonstrate that the deletion of the phoP/phoQ locus in S. typhi significantly attenuates this human pathogen.
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