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Infection and Immunity, July 1999, p. 3437-3443, Vol. 67, No. 7
Medical Division, United States Army Medical
Research Institute for Infectious Diseases, Fort Detrick, Maryland
217021; Division of Communicable
Diseases and Immunology, Walter Reed Army Institute of Research,
Washington, D.C. 203072; Post 02149, Israel Defense Force Medical Corps,
Israel3; and Unité de
Pathogénie Microbienne Moléculaire, Unité U389 de
l'Institut National de la Santé et de la Recherche
Médicale, Institut Pasteur, 75015, Paris,
France4
Received 23 December 1998/Returned for modification 15 February
1999/Accepted 12 April 1999
The Shigella flexneri 2a SC602 vaccine candidate
carries deletions of the plasmid-borne virulence gene icsA
(mediating intra- and intercellular spread) and the chromosomal locus
iuc (encoding aerobactin) (S. Barzu, A. Fontaine,
P. J. Sansonetti, and A. Phalipon, Infect. Immun. 64:1190-1196,
1996). Dose selection studies showed that SC602 causes shigellosis in a
majority of volunteers when 3 × 108 or 2 × 106 CFU are ingested. In contrast, a dose of
104 CFU was associated with transient fever or mild
diarrhea in 2 of 15 volunteers. All volunteers receiving single doses
of
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Vaccination against Shigellosis with Attenuated
Shigella flexneri 2a Strain SC602


104 CFU excreted S. flexneri 2a, and this
colonization induced significant antibody-secreting cell and
enzyme-linked immunosorbent assay responses against S. flexneri 2a lipopolysaccharide in two-thirds of the vaccinees.
Seven volunteers who had been vaccinated 8 weeks earlier with a single
dose of 104 CFU and 7 control subjects were challenged with
2 × 103 CFU of virulent S. flexneri 2a
organisms. Six of the control volunteers developed shigellosis with
fever and severe diarrhea or dysentery, while none of the vaccinees had
fever, dysentery, or severe symptoms (P = 0.005).
Three vaccinees experienced mild diarrhea, and these subjects had lower
antibody titers than did the fully protected volunteers. Although the
apparent window of safety is narrow, SC602 is the first example of an
attenuated S. flexneri 2a candidate vaccine that provides
protection against shigellosis in a stringent, human challenge model.
*
Corresponding author. Mailing address: Department of
Enteric Infections, Walter Reed Army Institute of Research,
Washington, DC 20307. Phone: (202) 782-3344. Fax: (202) 782-3299. E-mail: Dr._Thomas_Hale{at}wrsmtp-ccmail.army.mil.
Present address: Joint Vaccine Acquisition Program, Fort Detrick, Md.
Present address: Pharma Division, F. Hoffman-Laroche,
Ltd., CH-4002 Basel, Switzerland.
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