Department of Immunology and Microbiology, Stanford University School of Medicine, Stanford, California, USA.
J Clin Invest. 2011 Aug;121(8):3109-19. doi: 10.1172/JCI57834. Epub 2011 Jul 25.
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.
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。老年人特别容易受到影响，部分原因是疫苗效力随年龄增长而减弱。这与诱导强烈血清抗体反应的能力下降有关。在这里，我们表明这是由于疫苗特异性抗体的数量减少，而不是抗体亲和力或亲合力的缺乏。我们通过 ELISPOT 测量了年轻人和老年人接种灭活季节性流感疫苗后 1 周疫苗特异性浆母细胞的水平。从大量培养的 B 细胞中产生浆母细胞衍生的多克隆抗体 (PPAb)，而从单个浆母细胞中产生重组单克隆抗体 (re-mAb)。老年人中疫苗特异性浆母细胞的频率和 PPAb 的浓度低于年轻人，而每个浆母细胞分泌的 IgG 产量没有差异。在两组之间，PPAb 和 re-mAb 的疫苗特异性总体亲和力或亲合力没有差异。相比之下，对灭活季节性流感疫苗诱导的抗体对不在疫苗中的 2009 年大流行 H1N1 病毒的反应性在老年人中高于年轻人。这些结果表明，老年人对流感疫苗的抗体反应较差主要是由于疫苗特异性抗体数量减少所致。它们还表明，接触史会影响接种诱导的抗体的交叉反应性。
