Tsuji Takao, Shimizu Takeshi, Sasaki Keiko, Shimizu Yoshiyasu, Tsukamoto Kentaro, Arimitsu Hideyuki, Ochi Sadayuki, Sugiyama Satoshi, Taniguchi Koki, Neri Paola, Mori Hiroshi
Department of Microbiology, Fujita Health University, School of Medicine, Toyoake, Aichi, Japan.
Vaccine. 2008 Jan 24;26(4):469-76. doi: 10.1016/j.vaccine.2007.11.038. Epub 2007 Dec 3.
Escherichia coli O157:H7 produces Stx1 and Stx2 causing severe diseases. Their B subunits (StxBs) are useful for a vaccine but exhibit low immunogenicity, especially Stx2B. Nasal vaccination with StxBs plus cholera toxin induces only serum anti-Stx1B antibodies in mice. However, nasal administration of a mutant of E. coli enterotoxin and His-tagged Stx2B induced serum antibodies neutralizing Stx2 in vitro or in vivo and mucosal IgA antibodies in lungs. As His-tagged Stx2B showed five or three polymers in gel filtration chromatography, His-tagged Stx2B forms smaller tertiary structure than the native one and is effective for preventing Stx2 toxemia as a nasal vaccine.
大肠杆菌O157:H7产生的志贺毒素1(Stx1)和志贺毒素2(Stx2)会引发严重疾病。它们的B亚基(StxBs)对疫苗有用,但免疫原性较低,尤其是Stx2B。用StxBs加霍乱毒素进行鼻腔接种仅在小鼠中诱导产生血清抗Stx1B抗体。然而,经鼻腔给予大肠杆菌肠毒素突变体和His标签化的Stx2B可在体外或体内诱导产生中和Stx2的血清抗体以及肺部的黏膜IgA抗体。由于His标签化的Stx2B在凝胶过滤色谱中显示为五聚体或三聚体,His标签化的Stx2B形成的三级结构比天然结构小,作为鼻腔疫苗对预防Stx2毒血症有效。