California Institute of Technology
NEUTRALIZING ANTIBODIES AGAINST CORONAVIRUSES
The SARS-CoV-2 virus has caused a world-wide pandemic resulting in a massive loss of lives and detrimental effects on the economies of most countries. We are using single-particle cryo-electron microscopy (cryo-EM) to solve structures of infection- and vaccination-induced antibodies complexed with the spike trimer of SARS-CoV-2 in order to elucidate the structural correlates of antibody-based immune protection. Structural comparisons allowed us to classify antibodies against the receptor-binding domain (RBD) of spike trimer into categories. These classifications and structural analyses provide rules for assigning current and future human RBD-targeting antibodies into classes, evaluating avidity effects, and suggesting combinations for clinical use, and provide insight into immune responses against SARS-CoV-2. Our structural studies have also guided the development of a potential pan-betacoronavirus vaccine. The vaccine approach involves co-display of diverse sets of RBDs from SARS-like beta coronaviruses (sarbecoviruses) on nanoparticles (mosaic-RBD-nanoparticles) that results in increased breadth of neutralizing responses in mice compared with nanoparticles presenting only SARS-CoV-2 RBDs. This modular vaccine platform could provide protection from SARS-CoV-2 as well as potential future emergent coronaviruses that could cause pandemics.