Broad protective RBD heterotrimer vaccines neutralize SARS-CoV-2 including Omicron sub-variants XBB/BQ.1.1/BF.7
Author summary SARS-CoV-2 variants continue to emerge and circulate. Omicron sub-variants show severe evasion of the immune response induced by early-approved vaccines. Bivalent mRNA vaccines (prototype and Omicron BA. 5) have been approved for use in the United States and other countries. However, the co-circulation of SARS-CoV-2 variants (such as BA. 5.2, BF. 7, BQ. 1.1 and XBB) poses a challenge to disease control. The next-generation of COVID-19 vaccines need to induce potent and broad-spectrum immune responses. Here, we demonstrate a design strategy for trivalent SARS-CoV-2 vaccines with RBD-heterotrimers, which are single protein molecules without any linker sequences or trimerization domain. Biochemical and cryo-EM structural characterization demonstrated the total epitope exposure of RBD-trimers. Animal experiments showed that RBD-heterotrimers induce broad-spectrum protective immune responses. As a proof-of-concept, this trivalent immunogen design strategy is promising and practical for preventing the continuous circulation of SARS-CoV-2. This study provides guidance for future vaccine design against coronavirus and other viruses such as the influenza and dengue viruses.
