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Infection and Immunity, December 2005, p. 8027-8032, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.8027-8032.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Community-Based Safety, Immunogenicity, and Transmissibility Study of the Shigella sonnei WRSS1 Vaccine in Israeli Volunteers

Nadav Orr,1 David E. Katz,2,{dagger} Jacob Atsmon,3 Paull Radu,3 Miri Yavzori,1 Tamar Halperin,1 Tamar Sela,1 Raid Kayouf,1 Zivit Klein,1 Ruhama Ambar,1 Dani Cohen,4 Marcia K. Wolf,2,{ddagger} Malabi M. Venkatesan,2 and Thomas L. Hale2*

Center for Vaccine Development and Evaluation, Medical Corps, Israel Defense Force, Tel-Aviv, Israel,1 Department of Enteric Infections, Walter Reed Army Institute of Research, Silver Spring, Maryland,2 Tel-Aviv Sourasky Medical Center Clinical Research Center, Tel-Aviv, Israel,3 Department of Epidemiology and Preventative Medicine, Tel-Aviv University, Tel-Aviv, Israel4

Received 3 June 2005/ Returned for modification 15 July 2005/ Accepted 16 August 2005

We describe the first community-based evaluation of Shigella sonnei strain WRSS1, a live, oral candidate vaccine attenuated by a 212-bp deletion in the virG (or icsA) plasmid virulence gene. Three single-dose regimens of WRSS1 (5 x 103 CFU, 2 x 104 CFU, and 4 x 105 CFU) were tested with cohorts of 15 adult volunteers. The vaccine was generally well tolerated at the 103- and 104-CFU doses. There were no fevers and there was one report of moderate diarrhea in 30 vaccinees; five additional vaccinees reported mild diarrhea. At the 105-CFU dose, there were two reports of low-grade fevers and four reports of moderate diarrhea. The geometric means for immunoglobulin A (IgA) antibody-secreting cells (ASC) against lipopolysaccharide (LPS) were 30, 75, and 193 ASC per 106 peripheral blood mononuclear cells (PBMC) for the 103-, 104-, and 105-CFU doses, respectively. The IgG means were 40, 46, and 135 ASC per 106 PBMC, respectively. The 104-CFU dose of WRSS1 gave the best balance of safety and immunogenicity, since all vaccinees had a significant IgA ASC response and 73% had a response of more than 50 ASC. The anti-LPS seroconversion rate (threefold) for IgA was 60% and the IgG rate was 27% for the 104-CFU cohort. Each vaccinee and a cohabitating household contact delivered daily perianal stool swabs for bacteriological culture. WRSS1 colonized vaccinees for a median of 5 days, and one individual excreted WRSS1 intermittently for 23 days. None of the 45 household contacts were colonized with WRSS1 after a cumulative 192 days of cohabitation with colonized vaccinees, suggesting that adventitious vaccine spread was not common in the community setting.

* Corresponding author. Mailing address: Walter Reed Army Institute of Research, Department of Enteric Infections, 503 Robert Grant Avenue, Silver Spring, MD 20910-7500. Phone: (301) 319-9178. Fax: (301) 319-9801. E-mail: Thomas.Hale{at}na.amedd.army.mil.

Editor: J. D. Clements

{dagger} Present address: Massachusetts Department of Public Health, Division of Epidemiology and Immunization, Jamaica Plain, Mass.

{ddagger} Present address: Department of Regulatory Affairs, Walter Reed Army Institute of Research, Silver Spring, Md.

Infection and Immunity, December 2005, p. 8027-8032, Vol. 73, No. 12
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.12.8027-8032.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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