Three highly pathogenic coronaviruses – SARS-CoV-1 in 2002, MERS-CoV in 2012, and SARS-CoV-2 in 2019 – from the genus Betacoronavirus emerged into immune naïve humans which underlines the global public health threat posed by Betacoronaviruses. A major focus of our work relates to the design of next generation “universal” coronavirus vaccines approaches. We developed chimeric spike mRNAs that protect in vivo against SARS-CoV-2 variants and bat zoonotic SARS1-related viruses. We have defined vulnerable regions in SARS-CoV-2 and bat SARS1-related spikes that are targets of human broadly neutralizing antibodies. The identification of highly conserved epitopes in the spike RBD led us to recently develop multivalent nanoparticle vaccines that express receptor binding domains (RBDs) from both SARS-related and MERS-related viruses. We recently demonstrated that a single vaccine protects in mice against both lethal SARS-CoV-1 and highly pathogenic MERS-CoV challenge and neutralized SARS-CoV-2 variants including XBB.1.5. A trivalent RBD nanoparticle vaccine elicits broadly cross-reactive antibodies. Thus, a single vaccine protects against Group 2B/2C Betacoronavirus challenge in mice.
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