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Plasmablast antibody repertoires in elderly influenza vaccine responders exhibit restricted diversity but increased breadth of binding across influenza strains
Clinical Immunology ( IF 4.5 ) Pub Date : 2018-02-02 , DOI: 10.1016/j.clim.2018.01.011
Chia-Hsin Ju , Lisa K. Blum , Sarah Kongpachith , Nithya Lingampalli , Rong Mao , Petter Brodin , Cornelia L. Dekker , Mark M. Davis , William H. Robinson

Seasonal influenza vaccines elicit antibody responses that can prevent infection, but their efficacy is reduced in the elderly. While a subset of elderly individuals can still mount sufficient vaccine-induced antibody responses, little is known about the properties of the vaccine-induced antibody repertoires in elderly as compared to young responders. To gain insights into the effects of aging on influenza vaccine-induced antibody responses, we used flow cytometry and a cell-barcoding method to sequence antibody heavy and light chain gene pairs expressed by individual blood plasmablasts generated in response to influenza vaccination in elderly (aged 70–89) and young (aged 20–29) responders. We found similar blood plasmablast levels in the elderly and young responders seven days post vaccination. Informatics analysis revealed increased clonality, but similar heavy chain V(D)J gene usage in the elderly as compared to young vaccine responders. Although the elderly responders exhibited decreased antibody sequence diversity and fewer consequential mutations relative to young responders, recombinant antibodies from elderly responders bound a broader range of influenza strain HAs. Thus elderly influenza vaccine responders mount plasmablast responses with restricted diversity but with an increased breadth of binding across influenza strains. Our results suggest that the ability to generate plasmablast responses encoding cross-strain binding antibodies likely represents a mechanism important to vaccine responses in the elderly.



中文翻译:

老年流感疫苗应答者中的成浆细胞抗体库显示出受限制的多样性,但跨流感毒株的结合广度增加

季节性流感疫苗可引发可预防感染的抗体反应,但在老年人中其功效会降低。尽管一部分老年人仍然可以进行足够的疫苗诱导的抗体反应,但与年轻反应者相比,对于老年人疫苗诱导的抗体库的性质知之甚少。为了深入了解衰老对流感疫苗诱导的抗体反应的影响,我们使用流式细胞仪和细胞条形码方法对老年人(老年人)针对流感疫苗接种产生的单个成浆细胞表达的抗体重链和轻链基因对进行测序。 70-89岁)和年轻人(20-29岁)。我们在接种疫苗7天后发现老年人和年轻应答者的血浆成浆细胞水平相似。信息学分析表明,克隆性有所提高,但与年轻的疫苗接种者相比,老年人的重链V(D)J基因使用率相似。尽管相对于年轻应答者,老年应答者表现出降低的抗体序列多样性和较少的相应突变,但是来自老年应答者的重组抗体结合了更广泛的流感病毒株HA。因此,老年流感疫苗应答者的成浆细胞应答具有有限的多样性,但跨流感菌株的结合广度增加。我们的结果表明,产生编码跨菌株结合抗体的成浆细胞反应的能力可能代表了一种对老年人疫苗反应重要的机制。尽管相对于年轻应答者,老年应答者表现出降低的抗体序列多样性和较少的相应突变,但是来自老年应答者的重组抗体结合了更广泛的流感病毒株HA。因此,老年流感疫苗应答者的成浆细胞应答具有有限的多样性,但跨流感菌株的结合广度增加。我们的结果表明,产生编码跨菌株结合抗体的成浆细胞反应的能力可能代表了一种对老年人疫苗反应重要的机制。尽管相对于年轻应答者,老年应答者表现出降低的抗体序列多样性和较少的相应突变,但是来自老年应答者的重组抗体结合了更广泛的流感病毒株HA。因此,老年流感疫苗应答者的成浆细胞应答具有有限的多样性,但跨流感菌株的结合广度增加。我们的结果表明,产生编码跨菌株结合抗体的成浆细胞反应的能力可能代表了一种对老年人疫苗反应重要的机制。因此,老年流感疫苗应答者的成浆细胞应答具有有限的多样性,但跨流感菌株的结合广度增加。我们的结果表明,产生编码跨菌株结合抗体的成浆细胞反应的能力可能代表了一种对老年人疫苗反应重要的机制。因此,老年流感疫苗应答者的成浆细胞应答具有有限的多样性,但跨流感菌株的结合广度增加。我们的结果表明,产生编码跨菌株结合抗体的成浆细胞反应的能力可能代表了一种对老年人疫苗反应重要的机制。

更新日期:2018-02-02
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