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婴幼儿期接种乙型流感嗜血杆菌结合疫苗后的长期免疫持久性和 B 细胞记忆及加强免疫反应

Long-term persistence of immunity and B-cell memory following Haemophilus influenzae type B conjugate vaccination in early childhood and response to booster.

机构信息

Oxford Vaccine Group, Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, United Kingdom.

出版信息

Clin Infect Dis. 2014 Apr;58(7):949-59. doi: 10.1093/cid/ciu001. Epub 2014 Jan 7.

DOI:10.1093/cid/ciu001
PMID:24403544
Abstract

BACKGROUND

Protection against Haemophilus influenzae type b (Hib), a rapidly invading encapsulated bacteria, is dependent on maintenance of an adequate level of serum antibody through early childhood. In many countries, Hib vaccine booster doses have been implemented after infant immunization to sustain immunity. We investigated the long-term persistence of antibody and immunological memory in primary-school children following infant (with or without booster) Hib vaccination.

METHODS

Anti-polyribosylribitol phosphate (PRP) immunoglobulin G (IgG) concentration and the frequency of circulating Hib-specific memory B cells were measured before a booster of a Hib-serogroup C meningococcal (MenC) conjugate vaccine and again 1 week, 1 month, and 1 year after the booster in 250 healthy children aged 6-12 years in an open-label phase 4 clinical study.

RESULTS

Six to 12 years following infant priming with 3 doses of Hib conjugate vaccine, anti-PRP IgG geometric mean concentrations were 3.11 µg/mL and 0.71 µg/mL and proportions with anti-PRP IgG ≥1.0 µg/mL were 79% and 43% in children who had or had not, respectively, received a fourth Hib conjugate vaccine dose (mean age, 3.9 years). Higher baseline and post-Hib-MenC booster responses (anti-PRP IgG and memory B cells) were found in younger children and in those who had received a fourth Hib dose.

CONCLUSIONS

Sustained Hib conjugate vaccine-induced immunity in children is dependent on time since infant priming and receipt of a booster. Understanding the relationship between humoral and cellular immunity following immunization with conjugate vaccines may direct vaccine design and boosting strategies to sustain individual and population immunity against encapsulated bacteria in early childhood. Clinical Trials Registration ISRCTN728588998.

摘要

背景

预防侵袭力强的荚膜细菌流感嗜血杆菌(Hib)依赖于婴幼儿期通过早期维持足够的血清抗体水平。在许多国家,为了维持免疫,在婴幼儿免疫接种后已实施 Hib 疫苗加强剂接种。我们研究了婴幼儿 Hib 疫苗接种后,在小学儿童中抗体和免疫记忆的长期持久性。

方法

在 Hib 血清群 C 脑膜炎球菌(MenC)结合疫苗加强剂接种前、接种后 1 周、1 个月和 1 年,我们在一项开放标签的 4 期临床试验中,测量了 250 名 6-12 岁健康儿童循环中 Hib 特异性记忆 B 细胞的频率和抗多聚核糖基核糖醇磷酸(PRP)免疫球蛋白 G(IgG)浓度。

结果

在婴幼儿接种 3 剂 Hib 结合疫苗后 6-12 年,分别接受和未接受第四剂 Hib 结合疫苗接种儿童的抗-PRP IgG 几何平均浓度分别为 3.11 µg/mL 和 0.71 µg/mL,抗-PRP IgG≥1.0 µg/mL 的比例分别为 79%和 43%(平均年龄 3.9 岁)。在年龄较小的儿童和接受第四剂 Hib 疫苗接种的儿童中,基础和 Hib-MenC 加强后反应(抗-PRP IgG 和记忆 B 细胞)更高。

结论

儿童 Hib 结合疫苗诱导的持续免疫依赖于婴幼儿期初始免疫接种和加强剂接种的时间。了解结合疫苗接种后体液和细胞免疫之间的关系,可能有助于指导疫苗设计和加强剂接种策略,以维持婴幼儿期个体和人群对荚膜细菌的免疫。临床试验注册 ISRCTN728588998。

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