Montaño-Hirose J A, Lafage M, Weber P, Badrane H, Tordo N, Lafon M
Unité de la Rage, Institut Pasteur, Paris, France.
Vaccine. 1993 Sep;11(12):1259-66. doi: 10.1016/0264-410x(93)90052-y.
A mouse model was designed to test in vivo the efficacy of rabies immune globulins and specific neutralizing monoclonal antibodies to prevent European bat lyssavirus 1 infection. Human or equine rabies immune globulins previously found to contain variable amounts of neutralizing bat lyssavirus crossreactive antibodies were passively transferred to mice receiving intramuscularly a lethal dose of bat lyssavirus type 1. Immune globulins did not protect mice well against bat lyssavirus 1 whereas they reduced the mortality caused by rabies virus. In contrast, mice inoculated with bat lyssavirus 1 or rabies virus survived when passively immunized with bat lyssavirus 1 specific monoclonal antibody (mAb 8-2). This monoclonal antibody, an IgG2 alpha, recognized an epitope located in the antigenic site IIa of rabies glycoprotein. A mutation replacing the lysine 198 by glutamate in a rabies variant abrogated sensitivity to this neutralizing antibody. Because of its broad neutralizing spectrum against wild virus isolates, including European bat lyssaviruses, this monoclonal antibody should be a good candidate for rabies immune globulin replacement. It could improve efficacy of rabies vaccination, used either alone or in conjunction with human rabies immune globulins or monoclonal antibody cocktail to supplement their lack of crossreactivity to European bat lyssavirus 1.
设计了一种小鼠模型，用于在体内测试狂犬病免疫球蛋白和特异性中和单克隆抗体预防欧洲蝙蝠狂犬病病毒1型感染的效果。先前发现含有不同数量的可中和蝙蝠狂犬病病毒交叉反应抗体的人或马狂犬病免疫球蛋白被被动转移至肌肉注射致死剂量蝙蝠狂犬病病毒1型的小鼠体内。免疫球蛋白不能很好地保护小鼠免受蝙蝠狂犬病病毒1型感染，而它们能降低狂犬病病毒引起的死亡率。相比之下，用蝙蝠狂犬病病毒1型特异性单克隆抗体（mAb 8-2）进行被动免疫时，接种了蝙蝠狂犬病病毒1型或狂犬病病毒的小鼠存活了下来。这种单克隆抗体是一种IgG2α，识别位于狂犬病糖蛋白抗原位点IIa的一个表位。狂犬病病毒变异体中赖氨酸198被谷氨酸取代的突变消除了对这种中和抗体的敏感性。由于其对包括欧洲蝙蝠狂犬病病毒在内的野生病毒分离株具有广泛的中和谱，这种单克隆抗体应该是替代狂犬病免疫球蛋白的良好候选物。它可以提高狂犬病疫苗接种的效果，无论是单独使用还是与人狂犬病免疫球蛋白或单克隆抗体混合物联合使用，以补充它们对欧洲蝙蝠狂犬病病毒1型缺乏交叉反应性的不足。
