MECHANISMS OF RABIES VIRUS NEUTRALIZATION
MECHANISMS OF RABIES VIRUS NEUTRALIZATION
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DOI：
10.1006/viro.1993.1261
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发表时间：
1993-05-01
期刊：
影响因子：
3.7
通讯作者：
RUIGROK, RWH
中科院分区：
文献类型：
--
作者：
FLAMAND, A;RAUX, H;RUIGROK, RWH
中和狂犬病病毒（CVS株）所需的免疫球蛋白数量使用特异于糖蛋白三个抗原位点的IgG和IgM单克隆抗体（MAb）进行估计。据估计，低于130个IgG或30个IgM结合/病毒粒子，感染性被完全保留。病毒表面上3个加标物平均1或2个IgG中和，9至10个加标物平均1个IgM中和。根据抗体的不同，每个加标物中1 - 3个IgG达到饱和，4 - 5个加标物中1个IgM达到饱和。这一结果得到了电子显微镜的证实。还研究了在ELISA中继续固定选择性单克隆抗体的抗中和突变体。在两种情况下，缺乏中和是由于每个病毒粒子结合的免疫球蛋白的最大数量低于中和剂量。然而，在一种情况下，突变体能够固定与亲本菌株相同数量的IgG，并且即使在饱和时也不被中和。还检查了抗体减少病毒附着到BSR细胞上的能力。在没有抑制附着和抑制20倍之间的每一个中间体都被发现;即使在最后一种情况下，附着的抑制也不足以解释中和的程度。未发现抗体识别的抗原位点与抑制水平之间存在相关性。IgM抑制附着超过IgG，并且一种IgG 2b抗体根本不抑制附着。用这种抗体饱和的病毒粒子与人工脂质体的融合被完全抑制，或者是特异性的，或者是因为病毒-抗体复合物没有附着到脂质体上。
The number of immunoglobulins necessary to neutralize rabies virus (CVS strain) was estimated using IgG and IgM monoclonal antibodies (MAb) specific to the three antigenic sites of the glycoprotein. It was estimated that below 130 IgG or 30 IgM bound per virions, infectivity was totally preserved. Neutralization occurred for an average of 1 or 2 IgG for 3 spikes and 1 IgM for 9 to 10 spikes on the virus surface. Saturation was obtained for 1 to 3 IgG per spike, depending on the antibody, and 1 IgM for 4 to 5 spikes. This result was confirmed by electron microscopy. Neutralization-resisting mutants which continued to fix the selecting MAb in ELISA were also investigated. In two cases, the lack of neutralization was due to the fact that the maximum number of immunoglobulins bound per virion was below the neutralizing dose. In one case, however, the mutant was able to fix the same number of IgG as the parental strain and was not neutralized, even at saturation. The capacity of the antibodies to reduce the attachment of the virus onto BSR cells was also examined. Every intermediate between no inhibition of the attachment and inhibition by a factor of 20 was found; even in this last case, inhibition of attachment was insufficient to explain the extent of neutralization. No correlation was found between the antigenic site recognized by the antibody and the level of inhibition. IgM inhibited attachment more than IgG and one IgG2b antibody did not inhibit attachment at all. The fusion of virions saturated with this antibody with artificial liposomes was totally inhibited, either specifically or because virus-antibody complexes did not attached to the liposomes.