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

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 x 10(5) or 3 x 10(6) colony forming units (CFU) of WRSS1 or placebo, 4 weeks apart; children additionally received 3 x 10(4) 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 x 10(6) CFU (P = .048). Significant increases of Th-17 and proinflammatory cytokines (TNF-alpha, G-CSF, MIP-1 beta), 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.