phoP/phoQ-deleted Salmonella typhi (Ty800) is a safe and immunogenic single-dose typhoid fever vaccine in volunteers

J Infect Dis. 1996 Jun;173(6):1408-14. doi: 10.1093/infdis/173.6.1408.

Abstract

The phoP/phoQ virulence regulatory genes of Salmonella typhi Ty2 were deleted, and the resultant strain (Ty800) was tested as a live attenuated typhoid fever vaccine in human volunteers. Groups of 2 or 3 subjects received single oral doses of 10(7), 10(8), 10(9), or 10(10) cfu. Two volunteers who received the largest dose had self-limited side effects; no bacteremias were detected. Ten of 11 subjects had evidence of intestinal immune responses to the vaccine as measured by increases in S. typhi lipopolysaccharide-specific IgA-secreting cells in peripheral blood samples. Humoral immune responses were measured and compared with those of control vaccinees who received 4 oral doses of S. typhi Ty21a. In the most sensitive assays, 9 of 11 volunteers and 5 of 8 Ty21a control vaccinees had evidence of IgG directed against S. typhi antigens. Ty800 is safe, and single oral doses are highly immunogenic in humans.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Bacterial / blood*
  • Bacterial Proteins / genetics
  • DNA, Bacterial / analysis
  • Feces / microbiology
  • Female
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin G / blood
  • Lipopolysaccharides
  • Male
  • Middle Aged
  • Salmonella typhi / genetics
  • Salmonella typhi / immunology*
  • Salmonella typhi / isolation & purification
  • Sequence Deletion
  • Typhoid-Paratyphoid Vaccines / administration & dosage*
  • Typhoid-Paratyphoid Vaccines / adverse effects
  • Typhoid-Paratyphoid Vaccines / genetics
  • Typhoid-Paratyphoid Vaccines / immunology
  • Vaccination
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / adverse effects
  • Vaccines, Attenuated / immunology
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / adverse effects
  • Vaccines, Synthetic / immunology

Substances

  • Antibodies, Bacterial
  • Bacterial Proteins
  • DNA, Bacterial
  • Immunoglobulin A
  • Immunoglobulin G
  • Lipopolysaccharides
  • PhoQ protein, Bacteria
  • Typhoid-Paratyphoid Vaccines
  • Vaccines, Attenuated
  • Vaccines, Synthetic
  • PhoP protein, Bacteria