Structural studies promote vaccine development – Lessons from African Swine Fever Virus

African swine fever virus (ASFV) poses a critical global threat to swine populations, causing catastrophic economic losses due to the absence of effective vaccines or antiviral therapies. Efforts to develop vaccines have long been hampered by an incomplete understanding of the structural organization and antigenic architecture of this exceptionally large and complex virus. Recent breakthroughs in cryo-electron microscopy (cryo-EM) have resolved the near-atomic architecture of ASFV, revealing a multilayered virion built around a T=277 icosahedral lattice, stabilized by the major capsid protein p72 and accessory components such as M1249L, p17, p49, and H240R. These structural advances offer a robust foundation for rational vaccine design, particularly through the identification of key capsid protein p72. Moreover, high-resolution structural analyses of antigen-antibody complexes have defined conserved conformational epitopes, enabling the development of subunit vaccines with cross-protective potential across diverse ASFV strains. Drawing on parallels from structure-guided vaccine development in viruses such as respiratory syncytial virus (RSV), SARS-CoV-2, and influenza, this commentary emphasizes how structural virology can move ASFV vaccine research from empirical approaches toward precision immunogen engineering. The integration of structural insight with immunological design principles represents a transformative strategy to overcome longstanding barriers in ASFV control and accelerate the development of safe, effective vaccines.