Safety and immunogenicity of the live oral auxotrophic Shigella flexneri SFL124 in volunteers.
The live, aromatic dependent Shigella flexneri Y vaccine strain SFL124, with a deleted aroD gene, was tested for safety and immunogenicity in 21 healthy adult volunteers. A single dose of 2 x 10(9) live bacteria was given orally to ten volunteers, whereas 11 received three doses every other day. The vaccine was excreted for 4.2 days and was well tolerated by 90.5% of the vaccinees. Only 2 of 21 (9.5%) after the first dose had a self-limiting diarrhoea lasting 1 day; of volunteers given one dose only 3 of 10 showed anti-lipopolysaccharide (LPS) and anti-invasion plasmid coded antigen (Ipa) responses in serum. A faecal antibody response to LPS and Ipa was seen in six and three persons, respectively. Volunteers given three doses reacted with serum anti-LPS (9/11) and anti-Ipa (5/11) antibody responses. In stool, anti-LPS and anti-Ipa responses were detected in nine and eight volunteers, respectively. A booster dose of 2 x 10(9) bacteria given to six volunteers in the three-dose group 9-10 months later elicited high stool sIgA responses, indicating a strong mucosal memory, and was accompanied by a short excretion period of SFL124 (1.8 versus 4.2 days, p less than 0.05). The vaccination also elicited antibody-secreting cell (ASC) responses against LPS in peripheral blood: the three doses of the vaccine resulted in a stronger response than did the single dose, while the booster dose elicited only a limited ASC response. Volunteers previously exposed to shigellae exhibited stronger anti-Ipa responses in serum and stool suggestive of an immunological memory to the Ipa. The results indicate that SFL124 is a safe live vaccine strain inducing specific immune responses against LPS and Ipa with a mucosal immune memory lasting for at least 9 months.
Li
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A
Karolinska Institute, Department of Clinical Bacteriology, Huddinge Hospital, Sweden.
Pál
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T
Forsum
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U
Lindberg
A A
AA
D000284:Administration, Oral; D000328:Adult; D000906:Antibodies / Q000276:immunology; D000918:Antibody Specificity; D000921:Antibody-Producing Cells / Q000276:immunology; D001428:Bacterial Vaccines / Q000009:adverse effects / Q000494:pharmacology*; D015153:Blotting, Western; D005243:Feces / Q000382:microbiology; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012763:Shigella flexneri / Q000235:genetics / Q000276:immunology*; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000276:immunology
D000906:Antibodies; D001428:Bacterial Vaccines; D007070:Immunoglobulin A; D014613:Vaccines, Attenuated