Klipstein F A, Engert R F, Short H B
Infect Immun. 1980 Apr;28(1):163-70. doi: 10.1128/iai.28.1.163-170.1980.
The protective effect of active immunization with a purified preparation of the polymyxin-release form of Escherichia coli heat-labile enterotoxin (LT), administered using a parenteral prime and peroral boosts given after ablation of gastric secretion by means of cimetidine, was assessed in gnotobiotic rats which were challenged by monocontamination with enterotoxigenic strains of E. coli. Water transport was evaluated by the in vivo marker perfusion technique at weekly intervals over a 3-week period after contamination. Water transport in unimmunized control rats was consistently in absorption in those contaminated by a nontoxigenic strain, in secretion during only week 2 in those contaminated by an LT(+)/- strain, in secretion during weeks 2 and 3 in those contaminated by an LT(+)/ST(+) (heat-stable enterotoxin) strain, and consistently in absorption in those contaminated by an -/ST(+) strain. Rats immunized with a booster dosage of 250 mug had a significant increase (P < 0.001) in net water absorption as compared to unimmunized rats, with values in the borderline range of absorption, when challenged with either the LT(+)/- or LT(+)/ST(+) strains. Rats immunized with a 10-fold-higher boosting dosage had a significant increase (P < 0.001) in net water absorption as compared to those boosted at the lower dosage; water absorption was within the normal range. There was no difference between the ileal bacterial counts of unimmunized and immunized rats challenged by the various strains. These observations indicate that this immunization program provides complete protection in an animal model against challenge by intestinal contamination with enterotoxigenic strains of E. coli which produce LT, either alone or in combination with ST.
通过西咪替丁消除胃酸分泌后,采用肠胃外初次免疫和经口加强免疫的方式,给予纯化的大肠杆菌不耐热肠毒素(LT)多粘菌素释放形式制剂进行主动免疫,对经产肠毒素大肠杆菌单菌污染攻击的悉生大鼠的保护作用进行了评估。在污染后的3周内,每周通过体内标记灌注技术评估水转运情况。未免疫的对照大鼠中,被非产毒菌株污染的大鼠水转运始终处于吸收状态;被LT(+)/-菌株污染的大鼠仅在第2周处于分泌状态;被LT(+)/ST(+)(耐热肠毒素)菌株污染的大鼠在第2周和第3周处于分泌状态;被-/ST(+)菌株污染的大鼠水转运始终处于吸收状态。与未免疫大鼠相比,用250微克加强剂量免疫的大鼠在用LT(+)/-或LT(+)/ST(+)菌株攻击时,净吸水量显著增加(P < 0.001),吸水量处于吸收的临界范围内。与低剂量加强免疫的大鼠相比,用高10倍加强剂量免疫的大鼠净吸水量显著增加(P < 0.001);吸水量在正常范围内。用各种菌株攻击的未免疫和免疫大鼠的回肠细菌计数没有差异。这些观察结果表明,该免疫方案在动物模型中为抵抗产LT的产肠毒素大肠杆菌单独或与ST联合引起的肠道污染攻击提供了完全保护。