Generation of H7N9-specific human polyclonal antibodies from a transchromosomic goat (caprine) system

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 T...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2019-01, Vol.9 (1), p.366-366, Article 366
Main Authors: Wu, Hua, Fan, Zhiqiang, Brandsrud, Michelle, Meng, Qinggang, Bobbitt, Molly, Regouski, Misha, Stott, Rusty, Sweat, Alexis, Crabtree, Jackelyn, Hogan, Robert J., Tripp, Ralph A., Wang, Zhongde, Polejaeva, Irina A., Sullivan, Eddie J.
Format: Article
Language:English
Subjects:
13/1
13/106
13/44
42
631/1647
631/1647/1511
Artificial chromosomes
Cattle
Domestic animals
Fetuses
Goats
Hemagglutinins
Humanities and Social Sciences
Immunization
Immunoglobulins
Influenza A
Leukocytes (mononuclear)
multidisciplinary
Nuclear transfer
Peripheral blood mononuclear cells
Polyclonal antibodies
Reagents
Science
Science (multidisciplinary)
Somatic cell nuclear transfer
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-36961-5