ORIGINAL RESEARCH article
Front. Immunol.
Sec. Microbial Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1679421
This article is part of the Research TopicZoonotic Bacterial Pathogens: Infection and Host InteractionView all 7 articles
In Vivo Engineering of Transgenic Mice for Systemic Human Neutralizing Antibody Production Against Staphylococcal Enterotoxin B
Provisionally accepted
Zhiyang JiangBeichen Jia
Hu Naijing
Mengmeng ZhangHe Xiao
Guojiang Chen
Jijun YuXinying LiBeifen Shen
Jiannan Feng*
Jing Wang*- Academy of Military Medical Sciences, Beijing, China
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ABSTRACT: Transgenic animal bioreactors provide a complementary strategy to traditional mammalian cell culture systems for the production of therapeutic human monoclonal antibodies (mAbs). Here we present a CRISPR/Cas9-mediated breakthrough in creating two novel genetically engineered (GE) mouse models with species-specific chromosomal integration of human anti-staphylococcal enterotoxin B (SEB) mAb genes at either the ROSA26 or Hipp11 (H11) safe-harbor loci - evolutionarily conserved genomic safe harbors (GSH). These genetically optimized animals demonstrated broad tissue capability for glycosylation-competent human antibodies, achieving exceptional secretion levels reaching 208 mg/L in serum, 43 mg/L in mammary secretions, 24 mg/L in saliva on average. The transgenic lines maintained this antibody production stability for >140 weeks without compromising animal viability, while preserving germline transmission fidelity through six successive generations. Furthermore, the highly glycosylated human antibodies derived from these genetic engineered mice exhibited high binding affinity to SEB (KD=0.108 nM for ROSA26; 0.154 nM for H11), providing comprehensive protection against SEB intoxication in vivo. This study opens avenues for utilizing transgenic animal bioreactors for large-scale production of fully human antibodies or disease-resistant livestock in the foreseeable future.
Keywords: Staphylococcal enterotoxin B (SEB), Genome-engineered bioreactors, CRISPR/Cas9, Human monoclonal antibody, Genomic safe harbors (ROSA26/H11)
Received: 04 Aug 2025; Accepted: 22 Oct 2025.
Copyright: © 2025 Jiang, Jia, Naijing, Zhang, Xiao, Chen, Yu, Li, Shen, Feng and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jiannan Feng, fengjiannan1970@qq.com
Jing Wang, jingw_biomed@163.com
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