title: Safety and immunogenicity study of the auxotrophic Shigella flexneri 2a vaccine SFL1070 with a deleted aroD gene in adult Swedish volunteers.
abstract: The live auxotrophic Shigella flexneri 2a vaccine strain SFL1070 with a deleted aroD gene was given orally to 37 adult Swedish volunteers who received three doses within 5 days. Each dose comprised 1 x 10(5) (n = 9), 1 x 10(7) (n = 10), 1 x 10(8) (n = 9) or 1 x 10(9) (n = 9) c.f.u. S. flexneri SFL1070. One volunteer vaccinated with 1 x 10(7) and three vaccinated with 1 x 10(8) c.f.u. reported mild gastrointestinal symptoms after the first dose. Vaccination with 1 x 10(9) c.f.u. caused abdominal pain and watery diarrhoea in four volunteers who all recovered spontaneously within 72 h. S. flexneri SFL1070 was not recovered from volunteers given 1 x 10(5) c.f.u., but was shed in faeces by six volunteers vaccinated with 1 x 10(7), by all nine vaccinated with 1 x 10(8), and by seven volunteers vaccinated with 1 x 10(9) c.f.u. The mean excretion time was 2.6 (range 0-4) days in the 1 x 10(8) and the 1 x 10(9) groups. Serum antibody responses against either S. flexneri 2a and Y lipopolysaccharides (LPSs) or Shigella invasion plasmid antigens (Ipa) were seen in eight volunteers vaccinated with 1 x 10(9) (p < 0.01 to p < 0.05 for mean relative titres of IgA and IgG against S. flexneri 2a and Y LPSs), in four vaccinated with 1 x 10(8), and in two and one volunteers each vaccinated with 1 x 10(7) and 1 x 10(5) c.f.u. of S. flexneri SFL1070. Intestinal sIgA responses to the same antigens were elicited in all volunteers in the 1 x 10(9) and the 1 x 10(8) groups, and in six and one volunteers vaccinated with 1 x 10(7) and 1 x 10(5) c.f.u., respectively. The sIgA responses against S. flexneri 2a and Y LPSs were significant in all but the 1 x 10(5) group (p < 0.01 to p < 0.05). Significant antibody-secreting cell (ASC) responses specific to S. flexneri 2a LPS were seen in peripheral blood from eight volunteers each in the 1 x 10(9) and 1 x 10(8) groups and from five volunteers vaccinated with 1 x 10(7) c.f.u. (p < 0.01 to p < 0.05). The number of volunteers showing anti-Shigella Ipa ASC responses in these groups were five (p < 0.01 to p < 0.05), three and one, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Karolinska Institute, Department of Immunology, Microbiology, Pathology and Infectious Diseases, Huddinge Hospital, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Kärnell
authors.forename: A
authors.initials: A
authors.lastname: Li
authors.forename: C R
authors.initials: CR
authors.lastname: Zhao
authors.forename: K
authors.initials: K
authors.lastname: Karlsson
authors.forename: B M
authors.initials: BM
authors.lastname: Nguyen
authors.forename: A A
authors.initials: AA
authors.lastname: Lindberg
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000917:Antibody Formation; D001428:Bacterial Vaccines / Q000009:adverse effects* / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D005243:Feces / Q000382:microbiology; D005260:Female; D017353:Gene Deletion; D005798:Genes, Bacterial; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007422:Intestines / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012763:Shigella flexneri / Q000276:immunology*; D013548:Sweden; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D001428:Bacterial Vaccines; D007371:Interferon-gamma