Safety and immunogenicity of WRSd1, a live attenuated Shigella dysenteriae type 1 vaccine candidate

被引：32
|
作者：
McKenzie, Robin [1 ]
Venkatesan, Malabi M. [2 ]
Wolf, Marcia K. [3 ]
Islam, Dilara [4 ]
Grahek, Shannon [1 ]
Jones, Andrea M. [1 ]
Bloom, Arlene [1 ]
Taylor, David N. [1 ]
Hale, Thomas L. [2 ]
Bourgeois, A. Louis [1 ]
机构：
[1] Johns Hopkins Univ, Ctr Immunizat Res, Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA
[2] Walter Reed Army Inst Res, Div Bacterial & Rickettsial Dis, Silver Spring, MD USA
[3] Walter Reed Army Inst Res, Dept Regulatory Affairs, Silver Spring, MD USA
[4] Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand
来源：
VACCINE | 2008年 / 26卷 / 26期
关键词：
Shigella; S; dysenteriae; live attenuated vaccine;
D O I：
10.1016/j.vaccine.2008.03.079
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Among Shigella serotypes Shigella dysenteriae type 1 produces the most severe disease, including cases of hemolytic-uremic syndrome and pandemic outbreaks. WRSd1 is a live S. dysenteriae 1 strain attenuated by deletion of the virG(icsA) gene, which encodes a protein that mediates intercellular spread and stxA, and stxB, which encode the Shiga toxin. In this Phase I trial five groups of eight subjects ingested escalating doses of WRSd1 ranging from 10(3) to 10(7) CFU. No subject experienced fever or shigellosis, but 20% had diarrhea. Approximately two-thirds of subjects developed an IgA-ASC response to LPS. Days of fecal shedding of the vaccine strain, but not dose ingested, correlated with stronger immune responses. These results suggest that to be effective an attenuated Shigella vaccine must colonize well. (C) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码：3291 / 3296
页数：6
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