Phase I evaluation of ΔvirG Shigella sonnei live, attenuated, oral vaccine strain WRSS1 in healthy adults

Karen L. Kotloff, David N. Taylor, Marcelo B. Sztein, Steven S. Wasserman, Genevieve A. Losonsky, James P. Nataro, Malabi Venkatesan, Antoinette Hartman, William D. Picking, David E. Katz, James D. Campbell, Myron M. Levine, Thomas L. Hale

Research output: Contribution to journalArticlepeer-review

Abstract

We conducted a phase I trial with healthy adults to evaluate WRSS1, a live, oral ΔvirG Shigella sonnei vaccine candidate. In a double-blind, randomized, dose-escalating fashion, inpatient volunteers received a single dose of either placebo (n = 7) or vaccine (n = 27) at 3 × 103 CFU (group 1), 3 × 104 CFU (group 2), 3 × 105 CFU (group 3), or 3 × 106 CFU (group 4). The vaccine was generally well tolerated, although a low-grade fever or mild diarrhea occurred in six (22%) of the vaccine recipients. WRSS1 was recovered from the stools of 50 to 100% of the vaccinees in each group. The geometric mean peak anti-lipopolysaccharide responses in groups 1 to 4, respectively, were 99, 39, 278, and 233 for immunoglobulin (IgA) antibody-secreting cell counts; 401, 201, 533, and 284 for serum reciprocal IgG titers; and 25, 3, 489, and 1,092 for fecal IgA reciprocal titers. Post-vaccination increases in gamma interferon production in response to Shigella antigens occurred in some volunteers. We conclude that WRSS1 vaccine is remarkably immunogenic in doses ranging from 103 to 106 CFU but elicits clinical reactions that must be assessed in further volunteer trials.

Original languageEnglish (US)
Pages (from-to)2016-2021
Number of pages6
JournalInfection and immunity
Volume70
Issue number4
DOIs
StatePublished - 2002

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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