Generation and epitope mapping of two distinct neutralizing mAb subsets targeting BVDV E2: a pan-pestivirus cross-reactive linear epitope and a BVDV-specific conformational epitope
Abstract
Bovine viral diarrhea virus (BVDV) is an important infectious pathogen responsible for substantial economic losses in the global cattle industry. The structural protein E2 serves as a major protective antigen of BVDV and is the main target for host neutralizing immune responses. However, its antigenic structure and epitope distribution remain poorly understood. Here, five novel monoclonal antibodies (mAbs) against the E2 protein of BVDV-1 were generated using hybridoma technology, and their reactivity patterns, biological properties, and recognized epitopes were systematically characterized. As a result, one mAb, TBH033, specifically reacted with BVDV, while four mAbs, TBH002, TBH004, TBH008, and TBH009, exhibited broad-spectrum reactivity against different subgenotypes of classical swine fever virus (CSFV) and BVDV, as well as E2 proteins from eight pestivirus species (BVDV-1, BVDV-2, BVDV-3, CSFV, BDV, PPeV, GPeV, and ovIT PeV). All five mAbs exhibited high binding affinity to the E2 protein and potent cross-neutralizing activity against BVDV strains of different subgenotypes. Epitope mapping with chimeric recombinant and site-mutated E2 proteins revealed that TBH002, TBH004, TBH008, and TBH009 recognized a linear epitope in the DA domain, comprising 70H, 72R, 74L and 76T as critical residues; TBH033 targeted a BVDV-specific conformational epitope in the DB domain, defined by the conserved amino acid motifs 103LCP105, 123GP124. These findings enrich our understanding of the antigenic structure of the E2 protein and may facilitate the design of E2-based diagnostic tools and vaccines.
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BibTeX
@article{bao2026generation,
title = {{Generation and epitope mapping of two distinct neutralizing mAb subsets targeting BVDV E2: a pan-pestivirus cross-reactive linear epitope and a BVDV-specific conformational epitope}},
author = {Fei Bao and Shijiang Mi and Zhongdi Liu and Shuchi Zhang and Meng Wu and Yixiao Zhang and Changchun Tu and Wenjie Gong},
journal = {Veterinary Research},
year = {2026},
month = oct,
doi = {10.1186/s13567-026-01852-5},
url = {https://hal.science/hal-05793441v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Generation and epitope mapping of two distinct neutralizing mAb subsets targeting BVDV E2: a pan-pestivirus cross-reactive linear epitope and a BVDV-specific conformational epitope
AU - Fei Bao
AU - Shijiang Mi
AU - Zhongdi Liu
AU - Shuchi Zhang
AU - Meng Wu
AU - Yixiao Zhang
AU - Changchun Tu
AU - Wenjie Gong
PY - 2026
DA - 2026/10/12
JO - Veterinary Research
DO - 10.1186/s13567-026-01852-5
UR - https://hal.science/hal-05793441v1
AB - Bovine viral diarrhea virus (BVDV) is an important infectious pathogen responsible for substantial economic losses in the global cattle industry. The structural protein E2 serves as a major protective antigen of BVDV and is the main target for host neutralizing immune responses. However, its antigenic structure and epitope distribution remain poorly understood. Here, five novel monoclonal antibodies (mAbs) against the E2 protein of BVDV-1 were generated using hybridoma technology, and their reactivity patterns, biological properties, and recognized epitopes were systematically characterized. As a result, one mAb, TBH033, specifically reacted with BVDV, while four mAbs, TBH002, TBH004, TBH008, and TBH009, exhibited broad-spectrum reactivity against different subgenotypes of classical swine fever virus (CSFV) and BVDV, as well as E2 proteins from eight pestivirus species (BVDV-1, BVDV-2, BVDV-3, CSFV, BDV, PPeV, GPeV, and ovIT PeV). All five mAbs exhibited high binding affinity to the E2 protein and potent cross-neutralizing activity against BVDV strains of different subgenotypes. Epitope mapping with chimeric recombinant and site-mutated E2 proteins revealed that TBH002, TBH004, TBH008, and TBH009 recognized a linear epitope in the DA domain, comprising 70H, 72R, 74L and 76T as critical residues; TBH033 targeted a BVDV-specific conformational epitope in the DB domain, defined by the conserved amino acid motifs 103LCP105, 123GP124. These findings enrich our understanding of the antigenic structure of the E2 protein and may facilitate the design of E2-based diagnostic tools and vaccines.
SN - 0928-4249
SN - 1297-9716
ER -