Safety and immunogenicity of the live oral auxotrophic Shigella flexneri SFL124 in volunteers

An Li, Tibor Pál, Urban Forsum, Alf A. Lindberg

Research output: Contribution to journalArticlepeer-review

45 Citations (Scopus)

Abstract

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 × 109 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 × 109 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 < 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.

Original languageEnglish
Pages (from-to)395-404
Number of pages10
JournalVaccine
Volume10
Issue number6
DOIs
Publication statusPublished - 1992
Externally publishedYes

Keywords

  • Shigella flexneri
  • humans
  • immunogenicity
  • oral vaccination
  • safety

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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