Aase A, Høiby E A, Michaelsen T E
Department of Vaccinology, National Institute of Public Health, Oslo, Norway.
Scand J Immunol. 1998 Apr;47(4):388-96. doi: 10.1046/j.1365-3083.1998.00319.x.
To study how the different immunoglobulin (Ig)G subclass antibodies may confer protection against systemic meningococcal disease, we isolated IgG1, IgG2 and IgG3 antibodies from plasma from vaccinees immunized with the Norwegian meningococcal outer membrane vesicle vaccine. Four IgG1, one IgG2 and four IgG3 preparations were purified. The IgG2 and IgG3 subclass preparations were free from contaminating subclasses, whereas the IgG1 preparations contained from 0 to 14% of IgG2 and/or IgG3. Immunoblotting against whole-cell meningococcal antigens showed broad specificities of the various preparations, both within and between subclasses. These subclass preparations were tested for opsonophagocytic and bactericidal activity. As targets we used two different variants of the meningococcal vaccine strain, with low (44/76-SL) and high (44/76-1) expression of the outer membrane protein Opc. Using polymorphonuclear leucocytes as effector cells in the presence of human complement, all three IgG subclass preparations revealed high, and similar, opsonophagocytic activities against 44/76-SL, whereas against 44/76-1 the IgG2 preparation showed a reduced activity and most IgG3 preparations were slightly more active than the IgG1 preparations. Regarding bactericidal activity, all the three subclasses were highly active against 44/76-SL. Against 44/76-1 the bactericidal activities were somewhat more varied: all IgG1 and three IgG3 preparations exhibited higher activities than against 44/76-SL. Due to the low concentration in the IgG2 preparations, only a weak activity was seen against 44/76-1. One IgG3 preparation that was highly opsonophagocytic revealed no bactericidal activity against either of the two bacterial variants examined. In conclusion, we have shown that the IgG subclass effector functions differ from person to person, but that antibodies of IgG1, IgG2 and IgG3 subclasses, judged by their behaviour in the functional tests, may all contribute to protection against meningococcal disease.
为研究不同免疫球蛋白（Ig）G亚类抗体如何提供针对全身性脑膜炎球菌病的保护作用，我们从接种挪威脑膜炎球菌外膜囊泡疫苗的受种者血浆中分离出IgG1、IgG2和IgG3抗体。纯化了4份IgG1、1份IgG2和4份IgG3制剂。IgG2和IgG3亚类制剂不含其他亚类的污染，而IgG1制剂含有0至14%的IgG2和/或IgG3。针对全细胞脑膜炎球菌抗原的免疫印迹显示，各制剂在亚类内和亚类间均具有广泛的特异性。对这些亚类制剂进行了调理吞噬和杀菌活性测试。我们使用脑膜炎球菌疫苗株的两种不同变体作为靶标，外膜蛋白Opc的表达水平较低（44/76-SL）和较高（44/76-1）。在人补体存在的情况下，使用多形核白细胞作为效应细胞，所有三种IgG亚类制剂对44/76-SL均显示出高且相似的调理吞噬活性，而针对44/76-1，IgG2制剂显示活性降低，大多数IgG3制剂比IgG1制剂活性略高。关于杀菌活性，所有三个亚类对44/76-SL均具有高活性。针对44/76-1，杀菌活性的差异更大：所有IgG1和三份IgG3制剂的活性均高于对44/76-SL的活性。由于IgG2制剂中的浓度较低，对44/76-表现出的活性较弱。一份具有高调理吞噬活性的IgG3制剂对所检测的两种细菌变体均无杀菌活性。总之，我们已经表明，IgG亚类效应功能因人而异，但根据其在功能测试中的表现判断，IgG1、IgG2和IgG3亚类的抗体可能都有助于预防脑膜炎球菌病。
