Outpatient studies of the safety and immunogenicity of an auxotrophic Escherichia coli K-12-Shigella flexneri 2a hybrid vaccine candidate, EcSf2a-2.
A phase II study was conducted in 244 volunteers at Fort Ord, CA, to determine the safety and immunogenicity of EcSf2a-2, a live, oral Shigella vaccine constructed by transfer of genes from Shigella flexneri to Escherichia coli K-12. In this placebo-controlled study, four doses of vaccine ranging from 2.3 to 9.0 x 10(8) colony-forming units were given on days 0, 3, 14 and 17. Vaccine shedding occurred from 1 to 3 days after each dose. The vaccine was well tolerated at every dose tested. Significant levels of IgA, IgG or IgM antibody-secreting cells (ASC) recognizing S. flexneri 2a lipopolysaccharide (LPS) were found in 94% of a volunteer subset tested 7 days after the first dose of EcSf2a-2. Seven days after the third dose, ASC were detected less often (57%), and were mainly IgA. Significant rises in serum antibody to LPS were detected in 37% of vaccine recipients.
Taylor
D N
DN
Department of Enteric Infections, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Phillip
D F
DF
Zapor
M
M
Trofa
A
A
Van de Verg
L
L
Hartman
A
A
Bendiuk
N
N
Newland
J W
JW
Formal
S B
SB
Sadoff
J C
JC
D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood; D000921:Antibody-Producing Cells; D001428:Bacterial Vaccines / Q000009:adverse effects* / Q000276:immunology; D004926:Escherichia coli / Q000235:genetics* / Q000276:immunology; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D008297:Male; D012763:Shigella flexneri / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000009:adverse effects* / Q000276:immunology
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D007070:Immunoglobulin A; D014614:Vaccines, Synthetic