SAB Biotherapeutics, Sioux Falls, SD, 57104, USA.
SAB Capra, LLC, Salt Lake City, UT, 84101, USA.
Sci Rep. 2019 Jan 23;9(1):366. doi: 10.1038/s41598-018-36961-5.
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.
为了解决人类多克隆抗体作为治疗剂和诊断试剂的未满足需求，我们在先前建立的转染色体（Tc）牛平台的基础上，开发了一种在血清中表达人类多克隆抗体的 Tc 山羊系统。在 Tc 山羊系统中，将包含整个种系配置中人类免疫球蛋白（Ig）基因库的人类人工染色体（HAC）引入到山羊的遗传结构中。我们通过将 HAC 转移到山羊胎儿成纤维细胞中，然后进行体细胞核移植来生产 Tc 山羊来实现这一目标。外周血单核细胞（PBMC）和 Tc 山羊血清中的基因和蛋白表达分析分别表明人类 Ig 基因和抗体的成功表达。此外，用灭活的甲型流感（H7N9）病毒对 Tc 山羊进行免疫接种，然后用 H7N9 血凝素 1（HA1）加强免疫，在体外诱导出具有高中和活性的针对 H7N9 病毒的人类抗体。作为一种小型有蹄类动物，Tc 山羊具有成本低、种群快速建立的优势，因此补充了 Tc 牛平台，以满足一系列医疗需求和诊断应用，这些应用需要小体积的人类抗体产品。
