title: Safety and immunogenicity of CVD 1208S, a live, oral DeltaguaBA Deltasen Deltaset Shigella flexneri 2a vaccine grown on animal-free media.
abstract: A previous Phase 1 trial demonstrated that Shigella flexneri 2a deleted in guaBA, sen and set (strain CVD 1208) is well-tolerated and immunogenic after a single oral dose of 10(8) or 10(9) CFU. To facilitate further clinical development, the strain was reconstructed using animal-free media to conform to regulatory guidelines, and designated CVD1208S. Healthy inpatient volunteers were randomized (double-blind) to receive a single oral dose of either CVD 1208S (10(8) [n = 7] or 10(9) [n = 7] CFU) or placebo (n = 2). Both vaccine dosage levels were generally well-tolerated. Anti-lipopolysaccharide responses, measured as IgA antibody secreting cells, serum IgG, or fecal IgA levels, occurred in 7 (100%), three (43%) and two (29%) subjects following inoculation with 10(9) CFU, respectively. Interferon gamma production in response to Shigella antigens was observed in 1 of 4 (25%) and 4 of 7 (57%) subjects, following inoculation with 10(8) and 10(9) CFU. We conclude that CVD 1208S retains a favorable safety and immunogenicity profile after reconstruction on animal-free media, comparable to that seen with CVD 1208, which was constructed on media containing animal products, and shows promise as a live, oral Shigella vaccine.
authors.affiliation: Department of Pediatrics , University of Maryland School of Medicine, Baltimore, Maryland, USA. kkotloff@medicine.umaryland.edu
authors.forename: Karen L
authors.initials: KL
authors.lastname: Kotloff
authors.forename: Jakub K
authors.initials: JK
authors.lastname: Simon
authors.forename: Marcela F
authors.initials: MF
authors.lastname: Pasetti
authors.forename: Marcelo B
authors.initials: MB
authors.lastname: Sztein
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Wooden
authors.forename: Sofie
authors.initials: S
authors.lastname: Livio
authors.forename: James P
authors.initials: JP
authors.lastname: Nataro
authors.forename: William C
authors.initials: WC
authors.lastname: Blackwelder
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Barry
authors.forename: Wendy
authors.initials: W
authors.lastname: Picking
authors.forename: Myron M
authors.initials: MM
authors.lastname: Levine
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D004311:Double-Blind Method; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D005260:Female; D006801:Humans; D008297:Male; D012449:Safety; D022281:Shigella Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry / Q000276:immunology*; D012763:Shigella flexneri / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D022281:Shigella Vaccines