Fig. 1. Design of epitope scaffolds that bind to broadly cross-reactive antibodies against the spike^815–823 peptide.

a Left: Structure of the pre-fusion spike trimer (individual monomers: blue, violet and pale green; glycans: gray; PDBid:6xr8), with the Receptor Binding Domain (RBD) (green), spike^815–823 peptide (red) and stem helix (orange) domains highlighted. Middle: Zoom of spike monomer with spike^815–823 peptide highlighted (red) showing key residues engaged by antibodies. Right: Structure of spike^815–823 peptide (red) bound to DH1058 mAb (gray) (PDBid:7tow). b Computational models of DH1058 (gray) bound to ESs FP-2, FP-10 and FP-15 (green) with the grafted epitope shown in red sticks. c Binding affinities of ESs and spike to DH1058 and DH1294 mAbs as determined by SPR. d Binding of spike and ES to diverse spike^815–823-targeting mAbs and their inferred precursors. e ELISA binding of DH1058 mAb to synthetic spike^815–823 peptides and representative ESs that contain alanine mutations at epitope residues critical for antibody recognition. Numbers in brackets indicate the equivalent position of the mutated epitope residues on spike. f Crystal structure of DH1058 mAb (gray) in complex with FP-15 (salmon) overlaid with the computational model of the ESs (green). Epitope residues are shown in sticks (model: red; crystal structure: salmon). Source data are provided as a Source Data file.