¹Shihezi University, School of Animal Science and Technology, Department of Animal Husbandry, 832000, Shihezi City, CHINA DOI : 10.9775/kvfd.2025.35553 As Bovine Viral Diarrhea Virus (BVDV) is widespread in cattle and often causes immunosuppression, it is essential to evaluate whether it interferes with the effectiveness of widely used live vaccines such as Brucella abortus A19. This study evaluated the impact of BVDV infection on the immunoprotective efficacy of the B. abortus A19 vaccine using co-infection models in mice and RAW264.7 macrophages. The animal experiments revealed that co-infection led to significantly higher splenic bacterial loads of B. abortus A19 on days 14, 42, and 56 post-infection (pi), along with an increased spleen index on days 14, 28, 42, and 56 pi, compared to B. abortus A19 single-infection group. Results from the cell model demonstrated that co-infection enhanced intracellular survival of B. abortus A19 and significantly upregulated IL-10 mRNA and protein levels while suppressing TNF-α mRNA. In contrast, B. abortus A19 single-infection group induced higher expression of IL-12 and IFN-γ compared to BVDV single-infection group or co-infected groups. In conclusion, BVDV infection compromises the protective efficacy of the B. abortus A19 vaccine by enhancing the intracellular survival of B. abortus A19 in macrophages and dysregulating the expression of immune-related cytokines. These findings highlight the importance of BVDV control in vaccination programs and provide new insights into the mechanisms underlying vaccine failure under co-infection conditions. Keywords : Coinfection, Cytokines, Immunity, Intracellular survivaldynamics