Coster T S, Hoge C W, VanDeVerg L L, Hartman A B, Oaks E V, Venkatesan M M, Cohen D, Robin G, Fontaine-Thompson A, Sansonetti P J, Hale T L
Medical Division, United States Army Medical Research Institute for Infectious Diseases, Fort Detrick, Maryland 21702, USA.
Infect Immun. 1999 Jul;67(7):3437-43. doi: 10.1128/IAI.67.7.3437-3443.1999.
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 x 10(8) or 2 x 10(6) CFU are ingested. In contrast, a dose of 10(4) CFU was associated with transient fever or mild diarrhea in 2 of 15 volunteers. All volunteers receiving single doses of >/=10(4) 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 10(4) CFU and 7 control subjects were challenged with 2 x 10(3) 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.
福氏志贺菌2a SC602候选疫苗缺失了质粒携带的毒力基因icsA（介导细胞内和细胞间传播）以及染色体位点iuc（编码气杆菌素）（S. Barzu、A. Fontaine、P. J. Sansonetti和A. Phalipon，《感染与免疫》64:1190 - 1196，1996年）。剂量选择研究表明，当摄入3×10⁸或2×10⁶CFU时，SC602会使大多数志愿者患志贺菌病。相比之下，10⁴CFU的剂量在15名志愿者中有2人出现短暂发热或轻度腹泻。所有接受≥10⁴CFU单剂量的志愿者都排出了福氏志贺菌2a，这种定植在三分之二的疫苗接种者中诱导了针对福氏志贺菌2a脂多糖的显著抗体分泌细胞和酶联免疫吸附测定反应。7名8周前接种了10⁴CFU单剂量疫苗 的志愿者和7名对照受试者接受了2×10³CFU的有毒力福氏志贺菌2a菌株的攻击。6名对照志愿者患上了伴有发热和严重腹泻或痢疾的志贺菌病，而疫苗接种者中无人出现发热、痢疾或严重症状（P = 0.005）。3名疫苗接种者出现轻度腹泻，这些受试者的抗体滴度低于完全受到保护的志愿者。尽管明显的安全范围较窄，但SC602是减毒福氏志贺菌2a候选疫苗的首个实例，在严格的人体攻击模型中可提供针对志贺菌病的保护。
