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

tetano

Editor, Senior Moderator
Sci Rep. 2019 Jan 23;9(1):366. doi: 10.1038/s41598-018-36961-5.
[h=1]Generation of H7N9-specific human polyclonal antibodies from a transchromosomic goat (caprine) system.[/h] Wu H[SUP]1,[/SUP][SUP]2[/SUP], Fan Z[SUP]3[/SUP], Brandsrud M[SUP]1[/SUP], Meng Q[SUP]3[/SUP], Bobbitt M[SUP]1[/SUP], Regouski M[SUP]3[/SUP], Stott R[SUP]3[/SUP], Sweat A[SUP]3[/SUP], Crabtree J[SUP]4[/SUP], Hogan RJ[SUP]4[/SUP], Tripp RA[SUP]4[/SUP], Wang Z[SUP]5[/SUP], Polejaeva IA[SUP]6[/SUP], Sullivan EJ[SUP]7,[/SUP][SUP]8[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] 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.


PMID: 30675003 DOI: 10.1038/s41598-018-36961-5







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