title: Phase 2 clinical trial of attenuated Salmonella enterica serovar typhi oral live vector vaccine CVD 908-htrA in U.S. volunteers.
abstract: Salmonella enterica serovar Typhi strain CVD 908-htrA is a live attenuated strain which may be useful as an improved oral typhoid vaccine and as a vector for cloned genes of other pathogens. We conducted a phase 2 trial in which 80 healthy adults received one of two dosage levels of CVD 908-htrA in a double-blind, placebo-controlled, crossover study. There were no differences in the rates of side effects among volunteers who received high-dose vaccine (4.5 x 10(8) CFU), lower-dose vaccine (5 x 10(7) CFU), or placebo in the 21 days after vaccination, although recipients of high-dose vaccine (8%) had more frequent diarrhea than placebo recipients (0%) in the first 7 days. Seventy-seven percent and 46% of recipients of high- and lower-dose vaccines, respectively, briefly excreted vaccine organisms in their stools. All blood cultures were negative. Antibody-secreting cells producing antilipopolysaccharide (LPS) immunoglobulin A (IgA) were detected in 100 and 92% of recipients of high- and lower-dose vaccines, respectively. Almost half the volunteers developed serum anti-LPS IgG. Lymphocyte proliferation and gamma interferon production against serovar Typhi antigens occurred in a significant proportion of vaccinees. This phase 2 study supports the further development of CVD 908-htrA as a single-dose vaccine against typhoid fever and as a possible live vector for oral delivery of other vaccine antigens.
authors.affiliation: Center for Vaccine Development, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA. ctacket@medicine.umaryland.edu
authors.forename: C O
authors.initials: CO
authors.lastname: Tacket
authors.forename: M B
authors.initials: MB
authors.lastname: Sztein
authors.forename: S S
authors.initials: SS
authors.lastname: Wasserman
authors.forename: G
authors.initials: G
authors.lastname: Losonsky
authors.forename: K L
authors.initials: KL
authors.lastname: Kotloff
authors.forename: T L
authors.initials: TL
authors.lastname: Wyant
authors.forename: J P
authors.initials: JP
authors.lastname: Nataro
authors.forename: R
authors.initials: R
authors.lastname: Edelman
authors.forename: J
authors.initials: J
authors.lastname: Perry
authors.forename: P
authors.initials: P
authors.lastname: Bedford
authors.forename: D
authors.initials: D
authors.lastname: Brown
authors.forename: S
authors.initials: S
authors.lastname: Chatfield
authors.forename: G
authors.initials: G
authors.lastname: Dougan
authors.forename: M M
authors.initials: MM
authors.lastname: Levine
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D001428:Bacterial Vaccines / Q000009:adverse effects / Q000276:immunology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005822:Genetic Vectors; D006360:Heat-Shock Proteins; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D033903:Periplasmic Proteins; D012485:Salmonella typhi / Q000276:immunology*; D012697:Serine Endopeptidases / Q000235:genetics*; D015164:Vaccines, Inactivated / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D006360:Heat-Shock Proteins; D033903:Periplasmic Proteins; D015164:Vaccines, Inactivated; D007371:Interferon-gamma; C061682:DegP protease; D012697:Serine Endopeptidases