Fig. 9.

SARS-CoV-2 mRNA antigen immunogenicity and vaccine design. Full-length S-protein or RBD as a vaccine immunogen has been widely confirmed to induce high-affinity neutralizing antibodies. SARS-CoV-2 S protein is intrinsically metastable and can be stabilized in a prefusion conformation by structure-based design.^549,550 Prefusion-stabilized SARS-CoV-2 Spike immunogen induces potent humoral and cellular immune responses.^551,552 The RBD peptide is one of the most promising targets to design candidate vaccines. However, RBD has a low molecular weight, which leads to its weak immunogenicity, and can be further improved by forming multimers. Multimerization of RBD protein using humanized IgG Fc,²⁸⁴ T4 trimerization (FD)²⁸⁵ or Ferritin²⁸⁶ have been shown to induce higher neutralizing antibody compared to monomeric antigens, which will provide us with new ideas for designing powerful mRNA vaccines