Safety and immunogenicity of CVD 1208S, a live, oral DeltaguaBA Deltasen Deltaset Shigella flexneri 2a vaccine grown on animal-free media.
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.
Kotloff
Karen L
KL
Department of Pediatrics , University of Maryland School of Medicine, Baltimore, Maryland, USA. kkotloff@medicine.umaryland.edu
Simon
Jakub K
JK
Pasetti
Marcela F
MF
Sztein
Marcelo B
MB
Wooden
Stacey L
SL
Livio
Sofie
S
Nataro
James P
JP
Blackwelder
William C
WC
Barry
Eileen M
EM
Picking
Wendy
W
Levine
Myron M
MM
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*
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D022281:Shigella Vaccines