A GTPV-Based Murine Model Recapitulating Key Features of Lumpy Skin Disease for Preclinical Vaccine Evaluation

The global spread of lumpy skin disease (LSD), a devastating cattle disease caused by the lumpy skin disease virus (LSDV), is hampered by the lack of a practical small animal model for vaccine evaluation. Here, we established a mouse model by challenging C57BL/6 mice with goatpox virus (GTPV), a close relative of LSDV. Intranasal inoculation with a high dose (10^4.5 TCID₅₀) of GTPV induced robust infection characterized by weight loss, fever, high viral loads in the lungs and livers, and significant pulmonary pathology including immune cell infiltration and alveolar wall thickening. Infected mice mounted potent humoral immunity, with rapid IgM and sustained IgG and GTPV-specific binding antibody responses. The infection also elicited a dynamic cellular immune response, marked by biphasic IFN-γ production and dose-dependent increases in IL-17A and TNF-α. This GTPV-based murine model effectively recapitulates critical aspects of LSDV pathogenesis and immunity, providing a valuable and accessible tool for the accelerated development and preclinical assessment of novel LSDV vaccines.