Vaccine based on immune evasion mutations integrated RBD protein have broad protection against SARS-CoV-2 [mRNA-seq]

Variants of SARS-CoV-2 continue to emerge and evade immunity, resulting in breakthrough infections in vaccinated populations. Continued vaccination with vaccines based on the antigens of newly emerged variants does not necessarily result in long-lasting protection. Thus, there is an urgent need for the development of vaccines with a broad spectrum of protective effects. In this study, we selected hotspot mutations in the receptor binding domain (RBD) based on immune escape properties and integrated them into the original RBD protein to obtain a complexed RBD protein (cRBD). We designed a total of three cRBD (cRBD1-3) and thoroughly evaluated their immunological properties. Compared with the BA.1 RBD protein, the cRBDs induced higher levels and broader spectrum of neutralizing antibodies, with cRBD3 being the best performer. In vivo protective capacity of cRBDs was further validated in Balb/c mice attacked by live virus. In order to investigate the reason for the broad protective efficacy of cRBD, whole blood from mice that had completed the immunization process was subjected to RNA sequencing. Transcriptome analysis revealed that the vaccine was able to stimulate an immune response.