Recombinant RBD-based subunit vaccines incorporating high-frequency mutation sites elicit cross-immunity and robust protection against SARS-CoV-2

Introduction: Severe Acute Respiratory Syndrome Coronavirus type 2 (SARS-CoV-2), a highly pathogenic coronavirus (CoV) belonging to Coronavirus B, has triggered outbreaks or pandemics. Currently, many variants of SARS-CoV-2 have evolved, which exhibit severe immune evasion and imprinting resistance to existing vaccines and cause infected individuals to develop Post-Acute Sequelae of SARS-CoV-2 (also termed Long-COVID). This underscores the public health importance of developing effective vaccines with broad-spectrum efficacy against the SARS-CoV-2 variant and other CoVs with pandemic potential. Results: In this study, we expressed three tandem-repeat dimeric recombinant RBD proteins using an insect-baculovirus expression system integrated with the high-frequency SARS-CoV-2 RBD mutation sites. We performed immunogenicity assessment and attack protection tests. The date showed that these innovative SARS-CoV-2 RBD recombinant protein vaccines could show varying degrees of cross-immunity response and potent protection against SARS-CoV-2. Conclusion: Overall, our results indicated that these recombinant RBD subunit vaccines could serves a promising platform for a universal vaccine against SARS-CoV-2 and its variants, and provide a new perspective for the design of other future pandemic vaccines.