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A Recombinant Live Attenuated Strain of Vibrio cholerae Induces Immunity against Tetanus Toxin andBordetella pertussis Tracheal Colonization Factor

机译:霍乱弧菌的重组减毒活株诱导针对破伤风毒素和百日咳博德特氏菌气管定居因子的免疫

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An attenuated strain of Vibrio cholerae was used as a carrier for the expression of heterologous antigens such as fragment C from tetanus toxin (TetC) and tracheal colonization factor fromBordetella pertussis (Tcf). In vitro, high levels of protein were obtained when the Escherichia coli nirBpromoter was used and the bacteria were grown with low aeration. Intranasal immunization of mice with IEM101 expressing TetC elicited serum vibriocidal activity and induced antibodies against tetanus toxin which were protective against lethal challenge with 10 times the 50% lethal dose of tetanus toxin. Bacterial viability was essential for the induction of anti-TetC antibodies. Intranasal administration of IEM101 expressing Tcf induced a significant reduction in bacterial colonization of the tracheas of mice challenged with wild-type B. pertussis. These data are in agreement with the putative role of Tcf in Bordetellatracheal colonization. In conclusion, we have demonstrated thatV. cholerae may be used as a live vector to deliver heterologous antigens in vivo and that protection to both systemic and local challenge may be achieved.
机译:霍乱弧菌的减毒株用作表达异源抗原的载体,如破伤风毒素(TetC)的片段C和百日咳博德特氏菌(emf)的气管定植因子)。在体外,使用大肠杆菌nirB 启动子并在低通气条件下培养细菌,可以得到高水平的蛋白质。用表达TetC的IEM101进行小鼠的鼻内免疫可引起血清杀线活性,并诱导抗破伤风毒素的抗体,以50倍的破伤风毒素致死剂量的10倍可以致命。细菌生存力对于诱导抗TetC抗体至关重要。鼻内施用表达Tcf的IEM101诱导野生型 B攻击的小鼠气管细菌定植显着减少。百日咳。这些数据与Tcf在 Bordetella 气管定植中的假定作用相吻合。总之,我们证明了 V。霍乱可作为活载体在体内递送异源抗原,并可实现对全身和局部攻击的保护。

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