SARS-CoV-2 Spike conformation: impact on Fc-mediated effector functions

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causative agent of the ongoing Coronavirus disease (COVID-19) pandemic, is highly contagious and has infected more than 125 million people worldwide and caused over 2.75 million deaths since its discovery. The type, dynamics and persistence of protective immune responses in individuals infected with SARS-CoV-2 is currently under scrupulous investigation. The viral target of this response is the highly immunogenic trimeric Spike (S) glycoprotein, which facilitates SARS-CoV-2 entry into host cells. The antiviral activities of SARS-CoV-2-specific antibodies goes beyond their neutralizing activities and include Fc-mediated effector functions. Unfortunately, these antibody functions remain relatively understudied compared to their neutralizing activities. Why is it important to better understand Fc-mediated effector functions? The main reason is that they represent attractive targets for therapeutic interventions and vaccine development. The work proposed here will provide a better understanding of the S glycoprotein conformation and its impact in Fc-mediated effector functions. Improved knowledge of these responses will be critical to expand our current understanding of the conformational landscape of the S glycoprotein and thus has the potential to identify new vulnerabilities that could be exploited therapeutically.