An African swine fever vaccine-like variant with multiple gene deletions caused reproductive failure in a Vietnamese breeding herd

African swine fever (ASF), an economically damaging disease in domestic pigs, has emerged in Vietnam since 2019. Vietnam is the only country granted licenses for developing and commercializing modified live-attenuated vaccines (LAVs) against the highly pathogenic ASF virus (ASFV). The nationwide implementation of LAVs in Vietnam for prophylaxis has likely influenced the viral genetic pool among the swine population. This study highlighted the incursion of a novel ASF vaccine-like variant into a non-vaccinated breeding herd. Retrospective epidemiology suggested a high replacement rate and improper biosecurity measures might introduce the disease into the herd. Affected gilts displayed non-to-mild symptoms, whereas gestational sows experienced reproductive disorders. Remarkably, severe ulcerative dermatitis in udders was observed in lactating sows 1-2 weeks postpartum. The ASF outbreak was significantly associated with reduced reproductive performance compared to the pre-outbreak period (P < 0.001). Genetic analysis revealed several virulence-associated gene deletions and a marker gene presence in the left variable region, consistent with the ASFV-G-∆MGF vaccine strain. Molecular detection and immunohistochemistry indicated viral antigens distributed in macrophage-like cells of the reproductive organs and affected udders. Microscopic findings implied massive necrotizing vasculitis with fibrinoid degeneration compatible with immune complex-induced lesions. In conclusion, naïve sows are highly susceptible to the novel ASF vaccine-like variant than gilts, underscoring improved biosecurity requirements when introducing replacement gilts and monitoring ASF vaccine-like variants.