Porcine antibodies reveal novel non-neutralizing universal epitopes on FMDV and their overlaps with neutralization sites.

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Tác giả: Xingwen Bai, Huifang Bao, Yimei Cao, Huiying Fan, Yuanfang Fu, Shenglin Huang, Shulun Huang, Dong Li, Fengjuan Li, Kun Li, Pinghua Li, Zengjun Lu, Xueqing Ma, Pu Sun, Ying Sun, Jian Wang, Tao Wang, Hong Yuan, Jing Zhang, Qiang Zhang, Qiongqiong Zhao, Zhixun Zhao

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: Netherlands : Veterinary microbiology , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 703368

Foot-and-mouth disease virus (FMDV) is highly infectious and lacks cross-protection among serotypes, with antibodies playing a key role in antiviral immunity. To map conserved epitopes on the FMDV surface that exhibit cross-serotype reactivity, we constructed a pig-specific B-cell receptor (BCR) library through single B-cell sorting and high-throughput sequencing. This led to the identification of 16 broadly reactive, non-neutralizing monoclonal antibodies (mAbs), with 10 targeting VP2 (pOTB-1, pOTB-10, pOTB-13, pOTB-33, pOTB-37, pONY-14, pONY-17, pONY-23, pONY-30, pONY-60) and 6 targeting VP3 (pOTB-6, pOTB-11, pOTB-22, pOTB-23, pONY-3, pONY-59). Among these, a novel free linear epitope was identified at the C-terminus of VP2, recognized by pOTB-1, with the minimal recognition motif "KE." Key residues, T53 and W101, within the complementarity-determining region (CDR) of the pOTB-1 heavy chain, interact with the carboxyl group of the C-terminal glutamate through hydrogen bonding, contributing to the free-form nature of the epitope. Competitive enzyme-linked immunosorbent assays (cELISA) showed that most non-neutralizing antibodies (nNAbs) interfered with the binding of neutralizing antibodies B82 (site 2) and C4 (site 4), confirming the overlap between non-neutralizing and neutralizing epitopes. It has been confirmed that nNAbs mediate antiviral activity in vivo through various mechanisms, such as the formation of immune complexes. These findings reveal new epitopes on VP2 and VP3 and their spatial overlap with neutralizing sites, enhancing our understanding of FMDV immunogenicity and providing novel targets for vaccine and therapeutic development.
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