Evaluation of a phoP/phoQ-deleted, aroA-deleted live oral Salmonella typhi vaccine strain in human volunteers

Vaccine. 1996 Jan;14(1):19-24. doi: 10.1016/0264-410x(95)00173-x.


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 doses 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 delta aroA delta phoP/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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3-Phosphoshikimate 1-Carboxyvinyltransferase
  • Administration, Oral
  • Adolescent
  • Adult
  • Alkyl and Aryl Transferases*
  • Antibodies, Bacterial / biosynthesis
  • Bacterial Proteins / genetics
  • Bacterial Vaccines / administration & dosage
  • Bacterial Vaccines / adverse effects
  • Bacterial Vaccines / genetics*
  • Drug Evaluation, Preclinical
  • Female
  • Gene Deletion*
  • Genes, Bacterial / immunology*
  • Humans
  • Male
  • Middle Aged
  • Salmonella typhi / genetics*
  • Salmonella typhi / immunology*
  • Transcription Factors / immunology
  • Transferases / genetics*
  • Transferases / immunology*
  • Typhoid Fever / prevention & control
  • Vaccines, Attenuated / adverse effects
  • Vaccines, Attenuated / genetics*
  • Vaccines, Attenuated / immunology


  • Antibodies, Bacterial
  • Bacterial Proteins
  • Bacterial Vaccines
  • PhoQ protein, Bacteria
  • Transcription Factors
  • Vaccines, Attenuated
  • PhoP protein, Bacteria
  • Transferases
  • Alkyl and Aryl Transferases
  • 3-Phosphoshikimate 1-Carboxyvinyltransferase