A phase I trial of WRSS1, a Shigella sonnei live oral vaccine in Bangladeshi adults and children

Rubhana Raqib, Protim Sarker, K. Zaman, Nur Haque Alam, Thomas F. Wierzba, Nicole Maier, Kaisar Talukder, Abdullah Hel Baqui, Akamol E. Suvarnapunya, Firdausi Qadri, Richard I. Walker, Alan Fix, Malabi M. Venkatesan

Research output: Contribution to journalArticle

Abstract

Shigella sonnei live vaccine candidate, WRSS1, which was previously evaluated in US, Israeli and Thai volunteers, was administered orally to Bangladeshi adults and children to assess its safety, clinical tolerability and immunogenicity. In a randomized, placebo-controlled, dose-escalation, age-descending study, 39 adults (18–39 years) and 64 children (5–9 years) were enrolled. Each adult cohort (n = 13) received one dose of 3x104, or three doses of 3 × 105 or 3 × 106 colony forming unit (CFU) of WRSS1 (n = 10) or placebo (n = 3). Each child cohort (n = 16) received one dose of 3x103, or three doses of 3x104, 3x105, or 3 × 106 CFU WRSS1 (n = 12) or placebo (n = 4). WRSS1 elicited mostly mild and transient reactogenicity events in adults and children. In the 3 × 106 dose group, 50% of the adults shed the vaccine; no shedding was seen in children. At the highest dose, 100% of adults and 40% of children responded with a ≥ 4-fold increase of S. sonnei LPS-specific IgA antibody in lymphocyte supernatant (ALS). At the same dose, 63% of adults and 70% of children seroconverted with IgA to LPS, while in placebo, 33% of adults and 18% of children seroconverted. Both the vaccinees and placebos responded with fecal IgA to LPS, indicating persistent exposure to Shigella infections. In conclusion, WRSS1 was found safe up to 106 CFU dose and immunogenic in adults and children in Bangladesh. These data indicate that live, oral Shigella vaccine candidates, including WRSS1 can potentially be evaluated in toddlers and infants (<2 years of age), who comprise the target population in an endemic environment.

Original languageEnglish (US)
Pages (from-to)1326-1337
Number of pages12
JournalHuman Vaccines and Immunotherapeutics
Volume15
Issue number6
DOIs
StatePublished - Jun 3 2019

Keywords

  • Bangladesh
  • Shigella sonnei vaccine
  • WRSS1
  • adult
  • children
  • endemic region
  • phase I trial

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

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  • Cite this

    Raqib, R., Sarker, P., Zaman, K., Alam, N. H., Wierzba, T. F., Maier, N., Talukder, K., Baqui, A. H., Suvarnapunya, A. E., Qadri, F., Walker, R. I., Fix, A., & Venkatesan, M. M. (2019). A phase I trial of WRSS1, a Shigella sonnei live oral vaccine in Bangladeshi adults and children. Human Vaccines and Immunotherapeutics, 15(6), 1326-1337. https://doi.org/10.1080/21645515.2019.1575165