Vermont C L, van Dijken H H, van Limpt C J P, de Groot R, van Alphen L, van Den Dobbelsteen G P J M
Laboratory for Vaccine Research. National Institute for Public Health and the Environment (RIVM), Bilthoven, The Netherlands.
Infect Immun. 2002 Feb;70(2):584-90. doi: 10.1128/IAI.70.2.584-590.2002.
The avidity maturation and immunoglobulin G (IgG) isotype distribution of antibodies after vaccination with a meningococcal B outer membrane vesicle (OMV) vaccine were evaluated as indicators of protective immunity. Pre- and postvaccination sera from 134 healthy toddlers (ages, 2 to 3 years) immunized with a monovalent meningococcal B OMV (serosubtype P1.7-2,4) vaccine adsorbed with AlPO(4) or Al(OH)(3) were analyzed by enzyme-linked immunosorbent assay (ELISA) methods. The children were vaccinated three times with intervals of 3 to 6 weeks between vaccinations or twice with an interval of 6 to 10 weeks between vaccinations. A booster was given after 20 to 40 weeks. The avidity index (AI) of antibodies increased significantly during the primary series of vaccinations and after the booster was given. No differences in AIs were found when the results obtained with the two vaccination schedules or with the two adjuvants were compared. After vaccination, IgG1 was the predominant IgG isotype, followed by IgG3. No IgG2 or IgG4 was detected. There was a strong correlation between serum bactericidal activity (SBA) and ELISA titers (r = 0.85 [P < 0.0001] for total IgG, r = 0.83 for IgG1 [P < 0.0001], r = 0.82 for IgG3 [P < 0.0001], and r = 0.84 [P < 0.0001] for the avidity titer). When two subgroups with similar anti-OMV IgG levels were compared before and after the booster vaccination, the higher AI after the booster vaccination was associated with significantly increased SBA. We concluded that avidity maturation occurs after vaccination with a monovalent meningococcal B OMV vaccine, especially after boosting, as indicated by a significant increase in the AI. Vaccination with the monovalent OMV vaccine induced mainly IgG1 and IgG3 isotypes, which are considered to be most important for protection against meningococcal disease. An increase in the AI of antibodies is associated with increased SBA, independent of the level of specific IgG and the IgG isotype distribution. Measuring the AI and IgG isotype distribution of antibodies after vaccination can be a supplementary method for predicting protective immunity for evaluation in future phase III trials with meningococcal serogroup B vaccines.
评估接种B群脑膜炎球菌外膜囊泡（OMV）疫苗后抗体的亲和力成熟情况和免疫球蛋白G（IgG）亚型分布，作为保护性免疫的指标。采用酶联免疫吸附测定（ELISA）方法，分析了134名健康幼儿（年龄2至3岁）接种单价吸附于磷酸铝（AlPO₄）或氢氧化铝（Al(OH)₃）的B群脑膜炎球菌OMV（血清亚型P1.7-2,4）疫苗前后的血清。这些儿童接种三次，接种间隔为3至6周，或接种两次，接种间隔为6至10周。在20至40周后给予加强针。在初次接种系列期间和给予加强针后，抗体的亲和力指数（AI）显著增加。比较两种接种方案或两种佐剂获得的结果时，未发现AI有差异。接种后，IgG1是主要的IgG亚型，其次是IgG3。未检测到IgG2或IgG4。血清杀菌活性（SBA）与ELISA滴度之间存在强相关性（总IgG的r = 0.85 [P < 0.0001]，IgG1的r = 0.83 [P < 0.0001]，IgG3的r = 0.8
