Establishment of a Shigella sonnei human challenge model in Thailand.

In order to establish a human challenge model of Shigella related disease for vaccine testing, a dose-escalating inpatient trial was performed. Three groups of 12 healthy adult volunteers were orally challenged with 93,440 and 1680 CFU of Shigella sonnei strain 53G. Subjects were admitted to the Vaccine Trial Centre (VTC) at Mahidol University in Bangkok, Thailand.

Comparative evaluation of the antibody in lymphocyte supernatant (ALS) and enzyme-linked immunospot (ELISPOT) assays for measuring mucosal immune responses to Shigella antigens.

Accurately assessing mucosal immune responses to candidate vaccines remains a technical challenge. ELISPOT is widely used as a surrogate of mucosal immune response by directly enumerating circulating antibody secreting cells (ASCs), while antibody in lymphocyte supernatant (ALS) titers the total amount of antibody secreted by ASC ex vivo using ELISA. ALS is more practical than ELISPOT because the ASC supernatant is frozen for ELISA that can be conducted at any time, with any antigen, and in any laboratory.

Safety, dose, immunogenicity, and transmissibility of an oral live attenuated Shigella flexneri 2a vaccine candidate (SC602) among healthy adults and school children in Matlab, Bangladesh.

In double-blind trials in Bangladesh, 88 adults, and 79 children (8-10 years) were randomized to receive either a single oral dose of 1 × 10(4), 1 × 10(5) or 1 × 10(6)CFU of SC602 (a live, attenuated Shigella flexneri 2a strain vaccine) or placebo. In the adult outpatient 1 × 10(6) CFU group, severe joint pain and body aches were reported by one and two vaccinees respectively. In the adult inpatient trial, SC602 was isolated from 3 volunteers, pre-vaccination antibody titers were high, and fourfold increases in serum IgG anti-LPS responses were observed in 2 of 5 subjects of the 1 × 10(6)CFU group.

Vaccination of children in low-resource countries against Shigella is unlikely to present an undue risk of reactive arthritis.

Shigellosis is a major cause of morbidity and mortality among children in low-resource countries. Promising vaccine strategies in development include genetically attenuated Shigella, killed whole cell vaccines, subcellular vaccines, and O-polysaccharide-protein conjugates. There is a concern that Shigella vaccines could either induce reactive arthritis or could prime vaccinees for arthritis after a subsequent exposure to the pathogen because shigellosis is associated with reactive arthritis, especially in patients expressing the HLA B27 histocompatibility antigen.

Safety and immunogenicity of WRSd1, a live attenuated Shigella dysenteriae type 1 vaccine candidate.

Among Shigella serotypes Shigella dysenteriae type 1 produces the most severe disease, including cases of hemolytic-uremic syndrome and pandemic outbreaks. WRSd1 is a live S. dysenteriae 1 strain attenuated by deletion of the virG(icsA) gene, which encodes a protein that mediates intercellular spread, and stxA and stxB, which encode the Shiga toxin.

Community-based safety, immunogenicity, and transmissibility study of the Shigella sonnei WRSS1 vaccine in Israeli volunteers.

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.

Detection of Shigella by a PCR assay targeting the ipaH gene suggests increased prevalence of shigellosis in Nha Trang, Vietnam.

Shigella spp. are exquisitely fastidious gram-negative organisms which frequently escape detection by traditional culture methods. To get a more complete understanding of the disease burden caused by Shigella in Nha Trang, Vietnam, real-time PCR was used to detect Shigella DNA.

Two studies evaluating the safety and immunogenicity of a live, attenuated Shigella flexneri 2a vaccine (SC602) and excretion of vaccine organisms in North American volunteers.

We report the first community-based evaluation of Shigella flexneri 2a strain SC602, a live, oral vaccine strain attenuated by deletion of the icsA (virG) plasmid virulence gene, given at 10(4) CFU. The primary objectives of this trial were to determine the safety and immunogenicity of the vaccine and to determine the duration of colonization. Four of 34 volunteers experienced transient fevers, and three reported diarrhea during the first 3 days of the study.

Construction, characterization, and animal testing of WRSd1, a Shigella dysenteriae 1 vaccine.

WRSd1 is a Shigella dysenteriae 1 vaccine containing deletions of the virG(icsA) gene required for intercellular spreading and a 20-kb chromosomal region encompassing the Shiga toxin genes (stxAB). WRSd1 was constructed from S. dysenteriae 1 strain 1617 that was originally isolated during the 1968 to 1969 epidemic of Shiga dysentery in Guatemala.

Phase I evaluation of delta virG Shigella sonnei live, attenuated, oral vaccine strain WRSS1 in healthy adults.

We conducted a phase I trial with healthy adults to evaluate WRSS1, a live, oral Delta virG Shigella sonnei vaccine candidate. In a double-blind, randomized, dose-escalating fashion, inpatient volunteers received a single dose of either placebo (n = 7) or vaccine (n = 27) at 3 x 10(3) CFU (group 1), 3 x 10(4) CFU (group 2), 3 x 10(5) CFU (group 3), or 3 x 10(6) CFU (group 4). The vaccine was generally well tolerated, although a low-grade fever or mild diarrhea occurred in six (22%) of the vaccine recipients.