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首页> 外文期刊>Scientific reports. >Generation of H7N9-specific human polyclonal antibodies from a transchromosomic goat (caprine) system
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Generation of H7N9-specific human polyclonal antibodies from a transchromosomic goat (caprine) system

机译：从转染色体山羊（山羊）系统中产生H7N9特异性人多克隆抗体

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摘要

To address the unmet needs for human polyclonal antibodies both as therapeutics and diagnostic reagents, building upon our previously established transchromosomic (Tc) cattle platform, we report herein the development of a Tc goat system expressing human polyclonal antibodies in their sera. In the Tc goat system, a human artificial chromosome (HAC) comprising the entire human immunoglobulin (Ig) gene repertoire in the germline configuration was introduced into the genetic makeup of the domestic goat. We achieved this by transferring the HAC into goat fetal fibroblast cells followed by somatic cell nuclear transfer for Tc goat production. Gene and protein expression analyses in the peripheral blood mononuclear cells (PBMC) and the sera, respectively, of Tc caprine demonstrated the successful expression of human Ig genes and antibodies. Furthermore, immunization of Tc caprine with inactivated influenza A (H7N9) viruses followed by H7N9 Hemagglutinin 1 (HA1) boosting elicited human antibodies with high neutralizing activities against H7N9 viruses in vitro. As a small ungulate, Tc caprine offers the advantages of low cost and quick establishment of herds, therefore complementing the Tc cattle platform in responses to a range of medical needs and diagnostic applications where small volumes of human antibody products are needed.
机译：为了解决人类多克隆抗体作为治疗试剂和诊断试剂的未满足需求，在我们先前建立的转染色体（Tc）牛平台上，我们在此报告了在其血清中表达人类多克隆抗体的Tc山羊系统的开发。在Tc山羊系统中，将以种系构型包含整个人类免疫球蛋白（Ig）基因组成的人类人工染色体（HAC）引入了家山羊的遗传构成。我们通过将HAC转移到山羊胎儿成纤维细胞中，然后通过体细胞核转移来生产Tc山羊来实现这一目标。 Tc鼠的外周血单个核细胞（PBMC）和血清中的基因和蛋白质表达分析分别证明了人Ig基因和抗体的成功表达。此外，先用灭活的甲型流感病毒（H7N9）继之以H7N9血凝素1（HA1）免疫Tc山羊，可在体外产生对H7N9病毒具有高中和活性的人抗体。作为小蹄类动物，Tc山羊具有低成本和快速建立牛群的优势，因此可满足需要少量人类抗体产品的一系列医疗需求和诊断应用，从而补充了Tc牛平台。

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