Guttormsen H K, Wetzler L M, Naess A
Medical Department B, Haukeland Hospital, University of Bergen, Norway.
Infect Immun. 1993 Nov;61(11):4734-42. doi: 10.1128/iai.61.11.4734-4742.1993.
We have determined the amounts of specific anti-class 3 outer membrane protein antibodies of immunoglobulin G (IgG), IgM, and IgA isotypes in patient sera during the course of meningococcal disease by using purified class 3 protein as the sensitizing antigen in an enzyme-linked immunosorbent assay. The class 3 protein was obtained from a variant of strain 44/76 (B:15:P1.7,16) lacking class 1 and class 4 outer membrane proteins. Serum samples from 25 patients with systemic meningococcal disease caused by organisms of various serotypes were collected during the course of disease. Seven of these patients had been immunized with a meningococcal outer membrane vesicle vaccine made from strain 44/76 prior to disease. An increase in specific anti-class 3 (type 15) outer membrane protein IgG antibodies was demonstrated in 22 of 25 patients (88%), regardless of the serotype of the infecting strain. This indicates that the specific anti-class 3 antibodies were reacting in part with epitopes not determined by the monoclonal antibodies used for serotyping. A considerable heterogeneity in antibody levels and IgG subclass response was seen. Most patients had low levels of anti-class 3 antibodies during the acute illness, with antibodies peaking during the second week of disease and returning to near baseline in sera collected 6 to 12 months after the onset of the disease. The majority of the specific anti-class 3 IgG antibodies were shown to bind to surface-exposed epitopes on the whole bacteria and to belong to IgG1 and IgG3. The highest anti-class 3 IgG peak levels were seen in patients infected with strains of the homologous serotype after vaccination with the meningococcal outer membrane vesicle vaccine, suggesting an anamnestic response. However, these patients were not protected from meningococcal disease after immunization.
我们通过在酶联免疫吸附试验中使用纯化的3类蛋白作为致敏抗原,测定了脑膜炎球菌病病程中患者血清中免疫球蛋白G(IgG)、IgM和IgA同种型的特异性抗3类外膜蛋白抗体的量。3类蛋白取自44/76菌株(B:15:P1.7,16)的一个变体,该变体缺乏1类和4类外膜蛋白。在疾病过程中收集了25例由各种血清型病原体引起的全身性脑膜炎球菌病患者的血清样本。其中7例患者在患病前已接种了由44/76菌株制成的脑膜炎球菌外膜囊泡疫苗。25例患者中有22例(88%)出现特异性抗3类(15型)外膜蛋白IgG抗体增加,无论感染菌株的血清型如何。这表明特异性抗3类抗体部分与用于血清分型的单克隆抗体未确定的表位发生反应。观察到抗体水平和IgG亚类反应存在相当大的异质性。大多数患者在急性疾病期间抗3类抗体水平较低,抗体在疾病的第二周达到峰值,并在疾病发作后6至12个月采集的血清中恢复到接近基线水平。大多数特异性抗3类IgG抗体显示与完整细菌表面暴露的表位结合,属于IgG1和IgG3。在接种脑膜炎球菌外膜囊泡疫苗后感染同源血清型菌株的患者中观察到最高的抗3类IgG峰值水平,提示存在回忆反应。然而,这些患者在免疫后并未免受脑膜炎球菌病的侵袭。