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Infection and Immunity, February 2004, p. 923-930, Vol. 72, No. 2
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.2.923-930.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Two Studies Evaluating the Safety and Immunogenicity of a Live, Attenuated Shigella flexneri 2a Vaccine (SC602) and Excretion of Vaccine Organisms in North American Volunteers

David E. Katz,1,{dagger} Trinka S. Coster,2,{ddagger} Marcia K. Wolf,1 Fernando C. Trespalacios,2,§ Dani Cohen,3 Guy Robins,4 Antoinette B. Hartman,1 Malabi M. Venkatesan,1 David N. Taylor,1,¶ and Thomas L. Hale1*

Department of Enteric Infections, Walter Reed Army Institute of Research, Silver Spring,1 United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland,2 Department of Epidemiology and Preventive Medicine, Tel Aviv University, Tel Aviv,3 Medical Corps, Israel Defense Forces, Israel4

Received 10 July 2003/ Returned for modification 3 September 2003/ Accepted 10 November 2003

We report the first community-based evaluation of Shigella flexneri 2a strain SC602, a live, oral vaccine strain attenuated by deletion of the icsA (virG) plasmid virulence gene, given at 104 CFU. The primary objectives of this trial were to determine the safety and immunogenicity of the vaccine and to determine the duration of colonization. Four of 34 volunteers experienced transient fevers, and three reported diarrhea during the first 3 days of the study. Half of the volunteers mounted a positive serum immunoglobulin A (IgA) response to S. flexneri lipopolysaccharide. All but one of the volunteers excreted the vaccine in their stools for 1 to 33 days, and this excretion was often intermittent. Data from the community-based study were supplemented with an inpatient trial in which three volunteers received 103 and nine received 104 CFU. All volunteers who received 103 CFU excreted SC602 and had an IgA antibody-secreting cell response. Two of these had a serum IgA response. Six of the nine volunteers who received 104 CFU excreted SC602. One vaccinee had a transient fever and two met the definition of diarrhea. Six volunteers that received 104 CFU had an antibody-secreting cell response, and four had a serum IgA response. SC602 has now been tested at 104 CFU in a total of 58 volunteers. The cumulative results of these clinical trials, reported here and previously (Coster et al., Infect. Immun. 67:3437-3443, 1999), have demonstrated that SC602 is a substantially attenuated candidate vaccine that can evoke protection against the most severe symptoms of shigellosis in a stringent human challenge model of disease.

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

Editor: W. A. Petri, Jr.

{dagger} Present address: Centers for Disease Control and Prevention, Atlanta, Ga.

{ddagger} Present address: Division of Experimental Therapeutics, WRAIR, Silver Spring, Md.

§ Present address: Madigan Army Medical Center, Tacoma, Wash.

Present address: Johns Hopkins University School of Public Health, Baltimore, Md.

Infection and Immunity, February 2004, p. 923-930, Vol. 72, No. 2
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.2.923-930.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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