title: Clinical acceptability and immunogenicity of CVD 908 Salmonella typhi vaccine strain.
abstract: An attenuated Salmonella typhi strain has been sought as an improved oral typhoid vaccine and as a carrier of protective antigens of other pathogens to make hybrid vaccines. Ideally, such a strain would be safe and induce protective immune responses after a single oral dose. CVD 908 is a mutant of S. typhi wild-type strain Ty2 with recombinant deletions in two genes, aroC and aroD. In phase 1 testing to date, this strain has not produced febrile responses or other significant adverse reactions in adult volunteers given doses of 5 x 10(4) to 5 x 10(7) organisms with sodium bicarbonate. In addition, after just a single oral dose of 5 x 10(7) colony-forming units, this strain induced IgG seroconversion to S. typhi lipopolysaccharide in 83% of vaccinees and stimulated specific IgA-secreting gut-derived lymphocytes in 100% of vaccinees. CVD 908 is a new oral typhoid vaccine that should be further investigated as a carrier for expressing foreign antigens in recombinant vaccine constructs.
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore 21201.
authors.forename: C O
authors.initials: CO
authors.lastname: Tacket
authors.forename: D M
authors.initials: DM
authors.lastname: Hone
authors.forename: G A
authors.initials: GA
authors.lastname: Losonsky
authors.forename: L
authors.initials: L
authors.lastname: Guers
authors.forename: R
authors.initials: R
authors.lastname: Edelman
authors.forename: M M
authors.initials: MM
authors.lastname: Levine
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000907:Antibodies, Bacterial / Q000032:analysis; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007136:Immunoglobulins; D008070:Lipopolysaccharides / Q000032:analysis / Q000276:immunology; D012485:Salmonella typhi / Q000276:immunology*; D014613:Vaccines, Attenuated / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D007136:Immunoglobulins; D008070:Lipopolysaccharides; D014613:Vaccines, Attenuated; C042866:antilipopolysaccharide antibodies