A platform for the rapid screening of equine immunoglobins F (ab)2 derived from single equine memory B cells able to cross-neutralize to influenza virus

文献类型： 外文期刊

第一作者： Lin, Yuezhi

作者： Lin, Yuezhi;Li, Hongxin;Zhang, Jiaqi;Guo, Xing;Guo, Wei;Wang, Yaoxin;Wang, XiaoJun;Wang, Yayu;Liu, Tong;Liao, Huaxin;Guo, Wei;Wang, XiaoJun;Liu, Xiangning;Liu, Xiangning;Huang, Shaoli

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关键词： Single B cells-based antibody platform; neutralizing antibodies; equine immunoglobulins F(ab)2; influenza viruses; vaccine design

期刊名称：EMERGING MICROBES & INFECTIONS （ 影响因子：7.5； 五年影响因子：7.2 ）

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年卷期： 2024 年 13 卷 1 期

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收录情况： SCI

摘要： Single B cells-based antibody platforms offer an effective approach for the discovery of useful antibodies for therapeutic or research purposes. Here we present a method for screening equine immunoglobins F(ab)2, which offers the potential advantage of reacting with multiple epitopes on the virus. Using equine influenza virus (EIV) as model, a hemagglutinin (HA) trimer was constructed to bait B cells in vaccinated horses. We screened 370 HA-specific B cells from 1 x 106 PBMCs and identified a diverse set of equine variable region gene sequences of heavy and light chains and then recombined with humanized Ig Fc. Recombinant equine Ig was then self-assembled in co-transfected 293 T cells, and subsequently optimized to obtain HA binding B-cell receptor (s). The recombinant antibodies exhibited a high binding affinity to the HA protein. Antibody H81 exhibited the highest cross neutralizing activities against EIV strains in vitro. Furthermore, it effectively protected EIV-challenged mice, resulting in significantly improved survival, reduced pulmonary inflammation and decreased viral titers. In silico predication identified a functional region of H81 comprising 27 key amino acids cross the main circulating EIV strains. The 12 amino acid residues in this region with the highest binding affinities were screened. Notably, the predicted epitopes of H81 encompassed the documented equine HA receptor binding site, validating its cross-neutralization. In summary, a rapid platform was successfully established to investigate the profiling of equine antigen-recognizing receptors (BCRs) following infection. This platform has the potential to optimize the screening of virus-neutralizing antibodies and aid in vaccine design.

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