Safety and immunogenicity of phoP/phoQ-deleted Salmonella typhi expressingHelicobacter pylori urease in adult volunteers

Salmonella typhi Ty800, deleted for the Salmonella phoP/phoQ virulence regu lon has been shown to be a safe and immunogenic single dose oral typhoid fe ver vaccine in volunteers. This promising Vaccine strain was modified to co nstitutively express a heterologous protein of Gram negative bacterial orig in, Helicobacter pylori urease subunits A and B, yielding S. typhi strain T y1033. Seven volunteers received single oral doses of greater than or equal to 10(10) colony forming units of Ty1033; an eighth volunteer received two doses 3 months apart. Side effects were similar to those observed previous ly in volunteers who received the unmodified vector Ty800. All volunteers h ad strong mucosal immune responses to vaccination as measured by increases in IgA-secreting cells in peripheral blood directed against S, typhi antige ns. Seven of eight volunteers had convincing seroconversion as measured by increases in serum IgG directed against S, typhi flagella and lipopolysacch aride antigens by ELISA. No volunteer had detectable mucosal or humoral imm une responses to the urease antigen after immunization with single doses of Ty1033. A. subset of three volunteers received an oral booster vaccination consisting of recombinant purified H. pylori urease A/B and E. coli heat l abile toxin adjuvant 15 days after immunization with Ty1033. None of three had detectable humoral or mucosal immune responses to urease. Expression of a stable immunogenic protein in an appropriately attenuated S. typhi vecto r did not engender detectable mucosal or systemic antibody responses; addit ional work will be needed to define variables important for immunogenicity of heterologous antigens carried by live S. typhi vectors in humans. (C) 19 99 Elsevier Science Ltd. All rights reserved.