Safety and immunogenicity of WRSd1, a live attenuated Shigella dysenteriae type 1 vaccine candidate

Robin McKenzie, Malabi M. Venkatesan, Marcia K. Wolf, Dilara Islam, Shannon Grahek, Andrea M. Jones, Arlene Bloom, David N. Taylor, Thomas L. Hale, A. Louis Bourgeois

Research output: Contribution to journalArticle

Abstract

Among Shigella serotypes Shigella dysenteriae type 1 produces the most severe disease, including cases of hemolytic-uremic syndrome and pandemic outbreaks. WRSd1 is a live S. dysenteriae 1 strain attenuated by deletion of the virG(icsA) gene, which encodes a protein that mediates intercellular spread, and stxA and stxB, which encode the Shiga toxin. In this Phase I trial five groups of eight subjects ingested escalating doses of WRSd1 ranging from 103 to 107 CFU. No subject experienced fever or shigellosis, but 20% had diarrhea. Approximately two-thirds of subjects developed an IgA-ASC response to LPS. Days of fecal shedding of the vaccine strain, but not dose ingested, correlated with stronger immune responses. These results suggest that to be effective an attenuated Shigella vaccine must colonize well.

Original languageEnglish (US)
Pages (from-to)3291-3296
Number of pages6
JournalVaccine
Volume26
Issue number26
DOIs
StatePublished - Jun 19 2008

Keywords

  • Live attenuated vaccine
  • S. dysenteriae
  • Shigella

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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    McKenzie, R., Venkatesan, M. M., Wolf, M. K., Islam, D., Grahek, S., Jones, A. M., Bloom, A., Taylor, D. N., Hale, T. L., & Bourgeois, A. L. (2008). Safety and immunogenicity of WRSd1, a live attenuated Shigella dysenteriae type 1 vaccine candidate. Vaccine, 26(26), 3291-3296. https://doi.org/10.1016/j.vaccine.2008.03.079