Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies
Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies
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DOI：
10.1172/jci57834
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发表时间：
2011-08-01
影响因子：
15.9
通讯作者：
He, Xiao-Song
中科院分区：
文献类型：
--
作者：
Sasaki, Sanae;Sullivan, Meghan;He, Xiao-Song
在季节性流感流行期间，疾病负担主要由幼儿和老年人承担。老年人尤其受到影响，部分原因是疫苗效力随年龄增长而减弱。这与诱导强烈的血清抗体反应能力降低有关。在此，我们表明这是由于疫苗特异性抗体数量减少，而非缺乏抗体亲和力或亲合力。我们在年轻和老年成年人接种灭活季节性流感疫苗1周后，通过酶联免疫斑点试验（ELISPOT）测量了疫苗特异性浆母细胞的水平。从大量培养的B细胞产生浆母细胞衍生的多克隆抗体（PPAbs），而从单个浆母细胞产生重组单克隆抗体（re - mAbs）。老年人中疫苗特异性浆母细胞的频率和PPAbs的浓度低于年轻成年人，而每个浆母细胞分泌的IgG产量没有差异。在两个年龄组之间，未检测到PPAbs和re - mAbs总体疫苗特异性亲和力或亲合力的差异。相反，灭活季节性流感疫苗诱导的抗体对2009年大流行H1N1病毒（该病毒未包含在疫苗中）的反应性在老年人中高于年轻人。这些结果表明，老年人对流感疫苗接种的抗体反应较差主要是由于疫苗特异性抗体数量减少。它们还表明，接触史影响疫苗接种诱导抗体的交叉反应性。
During seasonal influenza epidemics, disease burden is shouldered predominantly by the very young and the elderly. Elderly individuals are particularly affected, in part because vaccine efficacy wanes with age. This has been linked to a reduced ability to induce a robust serum antibody response. Here, we show that this is due to reduced quantities of vaccine-specific antibodies, rather than a lack of antibody avidity or affinity. We measured levels of vaccine-specific plasmablasts by ELISPOT 1 week after immunization of young and elderly adults with inactivated seasonal influenza vaccine. Plasmablast-derived polyclonal antibodies (PPAbs) were generated from bulk-cultured B cells, while recombinant monoclonal antibodies (re-mAbs) were produced from single plasmablasts. The frequency of vaccine-specific plasmablasts and the concentration of PPAbs were lower in the elderly than in young adults, whereas the yields of secreted IgG per plasmablast were not different. Differences were not detected in the overall vaccine-specific avidity or affinity of PPAbs and re-mAbs between the 2 age groups. In contrast, reactivity of the antibodies induced by the inactivated seasonal influenza vaccine toward the 2009 pandemic H1N1 virus, which was not present in the vaccine, was higher in the elderly than in the young. These results indicate that the inferior antibody response to influenza vaccination in the elderly is primarily due to reduced quantities of vaccine-specific antibodies. They also suggest that exposure history affects the cross-reactivity of vaccination-induced antibodies.