摘要：SummaryVaccine development is challenged by the hierarchy of immunodominance between target antigen epitopes and the emergence of antigenic variants by pathogen mutation. The strength and breadth of antibody responses relies on selection and mutation in the germinal center and on the structural similarity between antigens. Computational methods for assessing the breadth of germinal center responses to multivalent antigens are critical to speed up vaccine development. Yet, such methods have poorly reflected the 3D antigen structure and antibody breadth. Here, we presentYmir, a new 3D-lattice-based framework that calculatesin silicoantibody-antigen affinities. Key physiological properties naturally emerge fromYmirsuch as affinity jumps, cross-reactivity, and differential epitope accessibility. We validatedYmirby replicating known features of germinal center dynamics. We show that combining antigens with mutated but structurally related epitopes enhances vaccine breadth.Ymiropens a new avenue for understanding vaccine potency based on the structural relationship between vaccine antigens.Graphical abstractDisplay OmittedHighlights•Fastin silicoantibody-antigen affinities to simulate multivalent vaccine response•Ymir recapitulates affinity jumps, cross-reactivity, and epitope accessibility•Possibility to simulate multivalent vaccine response using antigen PDB structure•Combining antigens with structurally related epitopes enhances vaccine breadthMolecular Structure; Immunology; Biocomputational method; Computer simulation
