Figure 1.

Schematic representation of different stages of the rational design of SARS‐CoV‐2 epitope‐scaffold proteins for immune‐focusing. Conserved and surface exposed spike epitopes were identified in steps 1 and 2. Suitable acceptor scaffold proteins were identified in step 3. Surface residues of the epitopes were grafted onto scaffold proteins (step 4) and stabilizing mutations incorporated (step 5). Confirmations of the grafted proteins were analyzed by DMD simulations (step 6). Stable proteins were expressed in E.coli and characterized by biophysical methods (steps 7 and 8). Five stable epitope‐scaffolds (step 9) were tested for immunogenicity and serological applications (steps 10 and 11).