Chatfield S N, Fairweather N, Charles I, Pickard D, Levine M, Hone D, Posada M, Strugnell R A, Dougan G
Vaccine Research Unit, Wellcome Research Labs, Beckenham, Kent, UK.
Vaccine. 1992;10(1):53-60. doi: 10.1016/0264-410x(92)90420-o.
The construction of a Salmonella typhi Ty2 strain harbouring defined deletions in both the aroA and aroC genes is described. These deletions have been fully defined at the molecular level by DNA sequencing and have been introduced in such a way that no foreign DNA remains in the S. typhi genome. This strain is attenuated in mice when given by the intraperitoneal route suspended in hog gastric mucin and is attenuated to a similar level to strains harbouring deletions in aroA or aroC alone indicating that both lesions are capable of attenuating independently. We have used this defined S. typhi aroA aroC strain to express stably a non-toxic 50 kDa fragment of tetanus toxin (fragment C) from a gene incorporated into the chromosome. This strain has the advantage of harbouring no antibiotic-resistance markers and we consider it to be a candidate bivalent oral typhoid-tetanus vaccine.
本文描述了一种伤寒沙门氏菌Ty2菌株的构建，该菌株的aroA和aroC基因均带有特定缺失。这些缺失已通过DNA测序在分子水平上得到充分界定，并且引入方式使得伤寒沙门氏菌基因组中不残留外源DNA。当以悬浮于猪胃粘蛋白中的腹腔注射途径给予小鼠时，该菌株减毒，且减毒程度与仅在aroA或aroC中带有缺失的菌株相似，这表明两个损伤均能独立减毒。我们已使用这种界定明确的伤寒沙门氏菌aroA aroC菌株，从整合到染色体中的基因稳定表达破伤风毒素的无毒50 kDa片段（片段C）。该菌株的优点是不携带抗生素抗性标记，我们认为它是一种候选二价口服伤寒-破伤风疫苗。
