Rare, high-affinity anti-pathogen antibodies from human repertoires, discovered using microfluidics and molecular genomics
Rare, high-affinity anti-pathogen antibodies from human repertoires, discovered using microfluidics and molecular genomics
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DOI：
10.1080/19420862.2017.1371383
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发表时间：
2017-01-01
期刊：
影响因子：
5.3
通讯作者：
Johnson, David S.
中科院分区：
文献类型：
--
作者：
Adler, Adam S.;Mizrahi, Rena A.;Johnson, David S.
亲和力成熟的功能性抗病原体抗体以低频率存在于天然人类库中。这些抗体通常是治疗性单克隆抗体的优秀候选物。然而，挖掘天然人抗体库是一个挑战。在这项研究中，我们展示了一种新的方法，该方法使用微流体，酵母展示和深度测序来识别247个天然配对的抗病原体单链可变片段（scFv），这些片段最初在人类谱系中罕见至10万分之一。甲型流感疫苗接种增加了甲型流感抗原结合scFv在外周B细胞库中的频率，
Affinity-matured, functional anti-pathogen antibodies are present at low frequencies in natural human repertoires. These antibodies are often excellent candidates for therapeutic monoclonal antibodies. However, mining natural human antibody repertoires is a challenge. In this study, we demonstrate a new method that uses microfluidics, yeast display, and deep sequencing to identify 247 natively paired anti-pathogen single-chain variable fragments (scFvs), which were initially as rare as 1 in 100,000 in the human repertoires. Influenza A vaccination increased the frequency of influenza A antigen-binding scFv within the peripheral B cell repertoire from