Functional antibodies and innate immune responses to WRSS1, a live oral Shigella sonnei vaccine candidate in Bangladeshi adults and children.

Background We have reported earlier 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 antibody responses. Here, we describe the functional antibodies and innate immune responses induced by WRSS1. Methods Adults (18-39 years) and children (5-9 years), received three doses of 3x10 5 or 3x10 6 colony forming unit (CFU) of WRSS1 or placebo, 4 weeks apart; children additionally received 3x10 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. Cyto/Chemokine concentrations were measured in lymphocyte cultures. Host defense peptides LL-37, human beta defensin-1 (HBD-1) and human defensin-5 (HD-5) were analyzed in plasma and stool. Results Children showed increased SBA titers over baseline after the 3 rd dose of 3x10 6 CFU (p=0.048). Significant increases of Th-17 and pro-inflammatory cytokines (TNF-α, G-CFS, MIP-1β), and reduction of anti-inflammatory and Th2 cytokines (IL-10, IL-13, GM-CSF) were observed in children. Plasma levels of HBD-1 and LL-37 decreased in children after vaccination but were increased/unchanged in adults. Conclusion Functional antibodies and Th1/Th17 cytokine responses in children may serve as important indicators of immunogenicity and protective potential of WRSS1.