Feng Pang, Shaobo Liang, Wei Zhou
Bovine viral diarrhea virus (BVDV) represents a significant global threat to the cattle industry, incurring major economic liabilities. Vaccination remains the cornerstone of BVDV management. This review synthesizes the evolution of BVDV vaccine development, ranging from conventional inactivated (IV) and modified live virus (MLV) vaccines to next-generation platforms, including recombinant subunit, vector-based, nucleic acid-based, and virus-like particle (VLP) vaccines. We critically compare these approaches regarding their immune responses, cross-protective efficacy, safety, and ability to prevent fetal persistent infection (PI). Significant challenges persist, notably the high genetic and antigenic variability of BVDV, the reservoir of PI animals, and maternal antibody interference. In conclusion, we emphasize the need to prioritize research into novel vaccine platforms, advanced adjuvants, and multivalent or combination vaccines that cover diverse BVDV sub-genotypes and co-pathogens. These strategies are essential for generating the broadly protective, cost-effective vaccines required to support global eradication efforts.