Identification of a novel monoclonal antibody derived from the lumpy skin disease virus ORF123 that confers cross-binding and cross-neutralizing activity against Capripoxvirus members

Capripoxviruses cause diseases (e.g., lumpy skin disease, sheep pox, and goat pox) that significantly hinder the growth of livestock production in endemic areas. Here, we systemically describe a B-cell monoclonal antibody (mAb) derived from the lumpy skin disease virus (LSDV) ORF123, which exhibits cross-reactivity with goat poxvirus (GTPV) and sheep poxvirus (SPPV). A novel continuous linear and conformational epitope, ⁸⁵PYFLKN⁹⁰, of LSDV and GTPV was first identified using bioinformatics, western blotting, and indirect immunofluorescence methods. Furthermore, the linear epitope recognition of SPPV by this LSDV ORF123 mAb was determined by the natural point mutation from P to Q at amino acid 85. Moreover, through alanine-scanning mutagenesis analysis, we demonstrated that the critical amino acid of this conserved linear and conformational epitope of LSDV ORF123 slightly differs from that of the GTPV homologue. Importantly, this mAb retained cross-neutralizing activity against LSDV, GTPV, and extracellular SPPV replication. The cross-binding and neutralizing activity of this LSDV ORF123 mAb strengthens our understanding of the pathogenic mechanisms and antigenic similarities among different members of the genus Capripoxviruses. These findings provide theoretical and experimental evidence for the development of universal pan-vaccines and therapeutic antibodies.