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表达与霍乱毒素A2/B亚基相连的链球菌粘附素的鼠伤寒沙门氏菌菌株的构建及其口服免疫原性

Construction and oral immunogenicity of a Salmonella typhimurium strain expressing a streptococcal adhesin linked to the A2/B subunits of cholera toxin.

作者信息

Hajishengallis G, Harokopakis E, Hollingshead S K, Russell M W, Michalek S M

机构信息

Department of Microbiology, University of Alabama at Birmingham 35294, USA.

出版信息

Vaccine. 1996 Nov;14(16):1545-8. doi: 10.1016/s0264-410x(96)00093-x.

DOI:10.1016/s0264-410x(96)00093-x
PMID:9014297
Abstract

A major adhesin from the oral pathogen Streptococcus mutans has been shown to be mucosally immunogenic upon genetic fusion with the cholera toxin A2/B subunits. To take advantage of the ability of Salmonella typhimurium to deliver cloned antigens to the mucosal inductive sites that would obviate the need for antigen purification, we expressed this chimeric construct in an attenuated S. typhimurium strain under the control of bacteriophage T7 transcription. Residual expression of the temperature-regulated T7 RNA polymerase at 30 degrees C allowed production of the chimeric protein at 2-3% of the total soluble protein, but it was increased five to six times following induction at 37 degrees C. Oral administration of a single dose of 10(9) recombinant Salmonella to mice resulted in serum IgG and salivary IgA antibody responses to Salmonella, cholera toxin, and the streptococcal adhesin, which were generally enhanced after a booster immunization.

摘要

已证明,口腔病原体变形链球菌的一种主要粘附素与霍乱毒素A2/B亚基进行基因融合后具有粘膜免疫原性。为利用鼠伤寒沙门氏菌将克隆抗原递送至粘膜诱导部位的能力(从而无需进行抗原纯化),我们在噬菌体T7转录的控制下,在一株减毒鼠伤寒沙门氏菌菌株中表达了这种嵌合构建体。在30℃时温度调节型T7 RNA聚合酶的残留表达使得嵌合蛋白的产量达到总可溶性蛋白的2-3%,但在37℃诱导后产量增加了五到六倍。给小鼠口服单剂量10⁹重组沙门氏菌后,会产生针对沙门氏菌、霍乱毒素和链球菌粘附素的血清IgG和唾液IgA抗体反应,加强免疫后这些反应通常会增强。

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Construction and oral immunogenicity of a Salmonella typhimurium strain expressing a streptococcal adhesin linked to the A2/B subunits of cholera toxin.表达与霍乱毒素A2/B亚基相连的链球菌粘附素的鼠伤寒沙门氏菌菌株的构建及其口服免疫原性
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