TY - JOUR
T1 - Vaccination against shigellosis with attenuated Shigella flexneri 2a strain SC602
AU - Coster, Trinka S.
AU - Hoge, Charles W.
AU - VanDeVerg, Lillian L.
AU - Hartman, Antoinette B.
AU - Oaks, Edwin V.
AU - Venkatesan, Malabi M.
AU - Cohen, Dani
AU - Robin, Guy
AU - Fontaine-Thompson, Annick
AU - Sansonetti, Philippe J.
AU - Hale, Thomas L.
PY - 1999
Y1 - 1999
N2 - 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 x 108 or 2 x 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 ≥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 x 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.
AB - 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 x 108 or 2 x 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 ≥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 x 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.
UR - http://www.scopus.com/inward/record.url?scp=0032968361&partnerID=8YFLogxK
U2 - 10.1128/iai.67.7.3437-3443.1999
DO - 10.1128/iai.67.7.3437-3443.1999
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AN - SCOPUS:0032968361
SN - 0019-9567
VL - 67
SP - 3437
EP - 3443
JO - Infection and Immunity
JF - Infection and Immunity
IS - 7
ER -