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Generation of H7N9-Specific Human Polyclonal Antibodies from a Transchromosomic Goat (caprine) System
Scientific Reports
  • Hua Wu, SAB Biotherapeutics
  • Zhiqiang Fan, Utah State University
  • Michelle Brandsrud, SAB Biotherapeutics
  • Qinggang Meng, Utah State University
  • Molly Bobbitt, SAB Biotherapeutics
  • Misha Regouski, Utah State University
  • Rusty Stott, Utah State University
  • Alexis Sweat, Utah State University
  • Jackelyn Crabtree, University of Georgia
  • Robert J. Hogan, University of Georgia
  • Ralph A. Tripp, University of Georgia
  • Zhongde Wang, Utah State University
  • Irina A. Polejaeva, Utah State University
  • Eddie J. Sullivan, SAB Biotherapeutics
Document Type
Article
Publisher
natureresearch
Publication Date
1-23-2019
Creative Commons License
Creative Commons Attribution 4.0
Disciplines
Abstract

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.

Citation Information
Wu, Hua, et al. "Generation of H7N9-specific human polyclonal antibodies from a transchromosomic goat (caprine) system." Scientific Reports, 9, 2019, pp. 1-9. https://doi.org/10.1038/s41598-018-36961-5