title: phoP/phoQ-deleted Salmonella typhi (Ty800) is a safe and immunogenic single-dose typhoid fever vaccine in volunteers.
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.
authors.affiliation: Infectious Disease Unit, Massachusetts General Hospital, Boston, USA.
authors.forename: E L
authors.initials: EL
authors.lastname: Hohmann
authors.forename: C A
authors.initials: CA
authors.lastname: Oletta
authors.forename: K P
authors.initials: KP
authors.lastname: Killeen
authors.forename: S I
authors.initials: SI
authors.lastname: Miller
mesh_terms: D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood*; D001426:Bacterial Proteins / Q000235:genetics; D004269:DNA, Bacterial / Q000032:analysis; D005243:Feces / Q000382:microbiology; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008070:Lipopolysaccharides; D008297:Male; D008875:Middle Aged; D012485:Salmonella typhi / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D017384:Sequence Deletion; D014436:Typhoid-Paratyphoid Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; C079792:PhoQ protein, Bacteria; D014436:Typhoid-Paratyphoid Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; C061064:PhoP protein, Bacteria