title: Community-based safety, immunogenicity, and transmissibility study of the Shigella sonnei WRSS1 vaccine in Israeli volunteers.
abstract: We describe the first community-based evaluation of Shigella sonnei strain WRSS1, a live, oral candidate vaccine attenuated by a 212-bp deletion in the virG (or icsA) plasmid virulence gene. Three single-dose regimens of WRSS1 (5 x 10(3) CFU, 2 x 10(4) CFU, and 4 x 10(5) CFU) were tested with cohorts of 15 adult volunteers. The vaccine was generally well tolerated at the 10(3)- and 10(4)-CFU doses. There were no fevers and there was one report of moderate diarrhea in 30 vaccinees; five additional vaccinees reported mild diarrhea. At the 10(5)-CFU dose, there were two reports of low-grade fevers and four reports of moderate diarrhea. The geometric means for immunoglobulin A (IgA) antibody-secreting cells (ASC) against lipopolysaccharide (LPS) were 30, 75, and 193 ASC per 10(6) peripheral blood mononuclear cells (PBMC) for the 10(3)-, 10(4)-, and 10(5)-CFU doses, respectively. The IgG means were 40, 46, and 135 ASC per 10(6) PBMC, respectively. The 10(4)-CFU dose of WRSS1 gave the best balance of safety and immunogenicity, since all vaccinees had a significant IgA ASC response and 73% had a response of more than 50 ASC. The anti-LPS seroconversion rate (threefold) for IgA was 60% and the IgG rate was 27% for the 10(4)-CFU cohort. Each vaccinee and a cohabitating household contact delivered daily perianal stool swabs for bacteriological culture. WRSS1 colonized vaccinees for a median of 5 days, and one individual excreted WRSS1 intermittently for 23 days. None of the 45 household contacts were colonized with WRSS1 after a cumulative 192 days of cohabitation with colonized vaccinees, suggesting that adventitious vaccine spread was not common in the community setting.
authors.affiliation: Center for Vaccine Development and Evaluation, Medical Corps, Israel Defense Force, Tel-Aviv, Israel.
authors.forename: Nadav
authors.initials: N
authors.lastname: Orr
authors.forename: David E
authors.initials: DE
authors.lastname: Katz
authors.forename: Jacob
authors.initials: J
authors.lastname: Atsmon
authors.forename: Paull
authors.initials: P
authors.lastname: Radu
authors.forename: Miri
authors.initials: M
authors.lastname: Yavzori
authors.forename: Tamar
authors.initials: T
authors.lastname: Halperin
authors.forename: Tamar
authors.initials: T
authors.lastname: Sela
authors.forename: Raid
authors.initials: R
authors.lastname: Kayouf
authors.forename: Zivit
authors.initials: Z
authors.lastname: Klein
authors.forename: Ruhama
authors.initials: R
authors.lastname: Ambar
authors.forename: Dani
authors.initials: D
authors.lastname: Cohen
authors.forename: Marcia K
authors.initials: MK
authors.lastname: Wolf
authors.forename: Malabi M
authors.initials: MM
authors.lastname: Venkatesan
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Hale
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000921:Antibody-Producing Cells / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics; D015331:Cohort Studies; D004405:Dysentery, Bacillary / Q000517:prevention & control; D005260:Female; D017353:Gene Deletion; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007557:Israel; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D022281:Shigella Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D012764:Shigella sonnei / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008070:Lipopolysaccharides; D022281:Shigella Vaccines; D014613:Vaccines, Attenuated