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开发一种杂交志贺全毒素类毒素疫苗,以引发针对1型和2型志贺毒素的异源保护。

Development of a hybrid Shiga holotoxoid vaccine to elicit heterologous protection against Shiga toxins types 1 and 2.

作者信息

Smith Michael J, Teel Louise D, Carvalho Humberto M, Melton-Celsa Angela R, O'Brien Alison D

机构信息

Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Room B4052, 4301 Jones Bridge Road, Bethesda, MD 20814-4799, USA.

出版信息

Vaccine. 2006 May 8;24(19):4122-9. doi: 10.1016/j.vaccine.2006.02.035. Epub 2006 Mar 3.

Abstract

The hemolytic uremic syndrome is a life-threatening sequela that occurs after infection with Shiga toxin (Stx)-producing Escherichia coli (STEC) or Shigella dysenteriae type 1, and Stx is responsible for initiating this syndrome. An STEC isolate can express Stx1, Stx2, or both, but antisera to Stx1 and Stx2 are not cross-neutralizing. To produce a single vaccine candidate against both toxins, we created a genetic toxoid that contained the enzymatically-inactivated StxA2 subunit and the native StxB1 subunit. We found that mice immunized with this hybrid holotoxoid, developed neutralizing anti-Stx1 and anti-Stx2 antibodies and survived challenge with 10 lethal doses of either or both toxins.

摘要

溶血尿毒综合征是一种在感染产志贺毒素(Stx)的大肠杆菌(STEC)或痢疾志贺菌1型后出现的危及生命的后遗症,志贺毒素是引发该综合征的原因。一株STEC分离株可以表达Stx1、Stx2或两者都表达,但针对Stx1和Stx2的抗血清不会交叉中和。为了制备一种针对两种毒素的单一候选疫苗,我们构建了一种基因类毒素,其包含经酶灭活的StxA2亚基和天然的StxB1亚基。我们发现,用这种杂交全毒素免疫的小鼠产生了中和性抗Stx1和抗Stx2抗体,并在受到10个致死剂量的任一毒素或两种毒素的攻击后存活下来。

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