We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Functional Antibodies and Innate Immune Responses to WRSS1, a Live Oral Shigella sonnei Vaccine Candidate, in Bangladeshi Adults and Children.
- Authors
Sarker, Protim; Mily, Akhirunnesa; Ara, Anjuman; Haque, Farjana; Maier, Nicole; Wierzba, Thomas F; Walker, Richard I; Venkatesan, Malabi M; Raqib, Rubhana
- Abstract
<bold>Background: </bold>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.<bold>Methods: </bold>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.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Subjects
BANGLADESH; ANTIMICROBIAL peptides; IMMUNE response; CLINICAL trial registries; IMMUNOGLOBULINS; SHIGELLA; CYTOKINES; RESEARCH; VACCINES; RESEARCH methodology; BACTERIAL antibodies; EVALUATION research; COMPARATIVE studies; RANDOMIZED controlled trials; IMMUNITY; SHIGELLOSIS; BANGLADESHIS; BACTERIAL vaccines
- Publication
Journal of Infectious Diseases, 2021, Vol 224, pS829
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiab395