title: Phase I clinical trials of aroA aroD and aroA aroD htrA attenuated S. typhi vaccines; effect of formulation on safety and immunogenicity.
abstract: PBCC211, an aroA aroD derivative of S. typhi strain CDC10-80, was tested in phase I trials as a single dose typhoid fever vaccine. Three different vaccine preparations, reconstituted lyophilized bacteria, freshly grown bacteria or lyophilized bacteria reconstituted from sachets, were orally administered to a total of 86 adult volunteers. An aroA aroD htrA strain, PBCC222, was also tested in 38 volunteers. Formulation impacted on the determination of a safe and immunogenic dose; reconstituted lyophilized cultures required higher doses than the broth cultures to stimulate seroconversion. In general, doses which seroconverted the majority of group members produced undesirable symptoms regardless of attenuation or formulation. The inability to separate the presence of symptoms from achieving significant immunogenicity in these aroA aroD or aroA aroD htrA strains precludes their use as single dose typhoid vaccines in the formulations tested. Multiple doses of these strains at a lower, safe level may be effective as vectors for foreign antigens.
authors.affiliation: Wyeth Vaccines, 211 Bailey Rd., West Henrietta, NY 14586-9728, USA.
authors.forename: D A
authors.initials: DA
authors.lastname: Dilts
authors.forename: I
authors.initials: I
authors.lastname: Riesenfeld-Orn
authors.forename: J P
authors.initials: JP
authors.lastname: Fulginiti
authors.forename: E
authors.initials: E
authors.lastname: Ekwall
authors.forename: C
authors.initials: C
authors.lastname: Granert
authors.forename: J
authors.initials: J
authors.lastname: Nonenmacher
authors.forename: R N
authors.initials: RN
authors.lastname: Brey
authors.forename: S J
authors.initials: SJ
authors.lastname: Cryz
authors.forename: K
authors.initials: K
authors.lastname: Karlsson
authors.forename: K
authors.initials: K
authors.lastname: Bergman
authors.forename: T
authors.initials: T
authors.lastname: Thompson
authors.forename: B
authors.initials: B
authors.lastname: Hu
authors.forename: A H
authors.initials: AH
authors.lastname: Brückner
authors.forename: A A
authors.initials: AA
authors.lastname: Lindberg
mesh_terms: D000293:Adolescent; D000328:Adult; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D018797:Cell Cycle Proteins / Q000008:administration & dosage* / Q000276:immunology; D005612:Freeze Drying; D006360:Heat-Shock Proteins; D006801:Humans; D008875:Middle Aged; D009994:Osmolar Concentration; D033903:Periplasmic Proteins; D012485:Salmonella typhi / Q000254:growth & development / Q000276:immunology*; D012697:Serine Endopeptidases / Q000235:genetics*; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology
chemical_list: D001428:Bacterial Vaccines; D018797:Cell Cycle Proteins; D006360:Heat-Shock Proteins; D033903:Periplasmic Proteins; D014613:Vaccines, Attenuated; C061682:DegP protease; D012697:Serine Endopeptidases