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脑膜炎奈瑟菌 C 群在荷兰人群中的免疫原性:脑膜炎球菌 C 结合疫苗引入前后的比较

Immunity against Neisseria meningitidis serogroup C in the Dutch population before and after introduction of the meningococcal c conjugate vaccine.

机构信息

Laboratory for Infectious Diseases and Screening, National Institute of Public Health and the Environment, Bilthoven, The Netherlands.

出版信息

PLoS One. 2010 Aug 13;5(8):e12144. doi: 10.1371/journal.pone.0012144.

Abstract

BACKGROUND

In 2002 a Meningococcal serogroup C (MenC) conjugate vaccine, with tetanus toxoid as carrier protein, was introduced in the Netherlands as a single-dose at 14 months of age. A catch-up campaign was performed targeting all individuals aged 14 months to 18 years. We determined the MenC-specific immunity before and after introduction of the MenC conjugate (MenCC) vaccine.

METHODS AND FINDINGS

Two cross-sectional population-based serum banks, collected in 1995/1996 (n = 8539) and in 2006/2007 (n = 6386), were used for this study. The main outcome measurements were the levels of MenC polysaccharide(PS)-specific IgG and serum bactericidal antibodies (SBA) after routine immunization, 4-5 years after catch-up immunization or by natural immunity. There was an increasing persistence of PS-specific IgG and SBA with age in the catch-up immunized cohorts 4-5 years after their MenCC immunization (MenC PS-specific IgG, 0.25 microg/ml (95%CI: 0.19-0.31 microg/ml) at age 6 years, gradually increasing to 2.34 microg/ml,(95%CI: 1.70-3.32 microg/ml) at age 21-22 years). A comparable pattern was found for antibodies against the carrier protein in children immunized above 9 years of age. In case of vaccination before the age of 5 years, PS-specific IgG was rapidly lost. For all age-cohorts together, SBA seroprevalence (> or =8) increased from 19.7% to 43.0% in the pre- and post-MenC introduction eras, respectively. In non-immunized adults the SBA seroprevalence was not significantly different between the pre- and post-MenC introduction periods, whereas PS-specific IgG was significantly lower in the post-MenC vaccination (GMT, age > or =25 years, 0.10 microg/ml) era compared to the pre-vaccination (GMT, age > or =25 years, 0.43 microg/ml) era.

CONCLUSION

MenCC vaccination administered above 5 years of age induced high IgG levels compared to natural exposure, increasing with age. In children below 14 months of age and non-immunized cohorts lower IgG levels were observed compared to the pre-vaccination era, whereas functional levels remained similar in adults. Whether the lower IgG poses individuals at increased risk for MenC disease should be carefully monitored. Large-scale introduction of a MenCC vaccine has led to improved protection in adolescents, but in infants a single-dose schedule may not provide sufficient protection on the long-term and therefore a booster-dose early in adolescence should be considered.

摘要

背景

2002 年,一种含有破伤风类毒素作为载体蛋白的脑膜炎奈瑟球菌 C 群(MenC)结合疫苗在荷兰被作为单剂疫苗用于 14 月龄儿童。我们针对所有 14 月龄至 18 岁的人群开展了补种运动。本研究旨在确定 MenC 结合疫苗(MenCC)接种前后的 MenC 特异性免疫情况。

方法和发现

本研究使用了两个基于人群的血清库,分别于 1995/1996 年(n=8539)和 2006/2007 年(n=6386)采集。主要观察指标为常规免疫接种后、补种免疫接种后 4-5 年或自然免疫后 MenC 多糖(PS)特异性 IgG 和血清杀菌抗体(SBA)的水平。在接受 MenCC 免疫接种的补种接种队列中,PS 特异性 IgG 和 SBA 随着年龄的增长而持续增加,4-5 年后(MenC PS 特异性 IgG,6 岁时为 0.25 microg/ml(95%CI:0.19-0.31 microg/ml),逐渐增加至 21-22 岁时的 2.34 microg/ml(95%CI:1.70-3.32 microg/ml))。在接种年龄超过 9 岁的儿童中,也观察到了针对载体蛋白的抗体具有类似的模式。在 5 岁以下儿童中接种疫苗,PS 特异性 IgG 会迅速消失。对于所有年龄队列,接种 MenC 前后的 SBA 血清阳性率(>或=8)分别从 19.7%增加到 43.0%。在未接种疫苗的成年人中,接种 MenC 前后的 SBA 血清阳性率无显著差异,而接种 MenC 疫苗(GMT,年龄>或=25 岁,0.10 microg/ml)后 PS 特异性 IgG 明显低于接种前(GMT,年龄>或=25 岁,0.43 microg/ml)。

结论

在 5 岁以上儿童中接种 MenCC 疫苗会诱导较高的 IgG 水平,与自然暴露相比,该水平随年龄增长而增加。在 14 个月以下的儿童和未接种疫苗的人群中,与接种前相比,观察到的 IgG 水平较低,而成年人的功能水平仍相似。较低的 IgG 是否会使个体患 MenC 疾病的风险增加,应密切监测。大规模引入 MenCC 疫苗已导致青少年的保护得到改善,但在婴儿中,单剂方案可能无法长期提供足够的保护,因此应考虑在青春期早期进行加强剂接种。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/24df/2921331/53d3a77bd9dc/pone.0012144.g001.jpg

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