Development of pan-betacoronavirus vaccines

The project addresses knowledge gaps in identifying CoV spike broadly neutralizing antibody (bnAb) sites and developing vaccine strategies for durable, protective bnAb responses. Aim #1 involves designing novel spike S2 stem bnAb site targeting vaccine immunogens using a rational reverse vaccine engineering approach, including peptide-based nanoparticles, engineered S2 bnAb germline-targeting S-protein trimer immunogens, and multimerized nanoparticle versions. Aim #2 focuses on iteratively evaluating and optimizing prime-boost immunization strategies in pre-clinical animal models to induce durable and protective bnAb responses against diverse β-CoVs, assessing in vivo protective efficacy in virus challenge models. Aim #3 will generate spike S2 stem helix bnAb based “super antibodies” against β-coronaviruses using rational antibody engineering approaches. The overall goal is to rationally design novel vaccine immunogen candidates, develop robust vaccination strategies, and create “super antibody” molecules for broad coronavirus intervention.