Dataset Information

Functional Antibodies and Innate Immune Responses to WRSS1, a Live Oral Shigella sonnei Vaccine Candidate, in Bangladeshi Adults and Children.

ABSTRACT:

Background

We demonstrated in a randomized placebo-controlled trial that WRSS1, a live oral Shigella sonnei vaccine candidate, is safe in Bangladeshi adults and children, and elicits antigen-specific antibodies. Here, we describe functional antibody and innate immune responses to WRSS1.

Methods

Adults (18-39 years) and children (5-9 years) received 3 doses of 3 × 105 or 3 × 106 colony forming units (CFU) of WRSS1 or placebo, 4 weeks apart; children additionally received 3 × 104 CFU. Blood and stool were collected at baseline and 7 days after each dose. Functional antibodies were measured using serum bactericidal antibody (SBA) assay. Cytokine/chemokine concentrations were measured in lymphocyte cultures. Host defense peptides LL-37, HBD-1, and HD-5 were analyzed in plasma and stool.

Results

Children showed increased SBA titers over baseline after the third dose of 3 × 106 CFU (P = .048). Significant increases of Th-17 and proinflammatory cytokines (TNF-α, G-CSF, MIP-1β), and reduction of anti-inflammatory and Th2 cytokines (IL-10, IL-13, GM-CSF) were observed in children. Plasma HBD-1 and LL-37 decreased in children after vaccination but were increased/unchanged in adults.

Conclusions

Functional antibodies and Th1/Th17 cytokine responses in children may serve as important indicators of immunogenicity and protective potential of WRSS1. Clinical Trials Registration: NCT01813071.

SUBMITTER: Sarker P

PROVIDER: S-EPMC8687094 | biostudies-literature |

REPOSITORIES: biostudies-literature

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