Antibody-dependent cellular cytotoxicity against SARS-CoV-2 variants of concern

In December 2019, several pneumonia outbreaks emerged in China, all related to the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The high transmissibility of SARS-CoV-2 caused the current devastating pandemic of coronavirus disease 2019 (COVID-19). Through a collective effort, around 7 billion vaccine doses were administered worldwide as of November 2021 and demonstrated high levels of protection against infections and severe cases of COVID-19. Most vaccines deployed target the spike (S) glycoprotein. The S protein is exposed at the surface of viral particles and infected cells. Its role is essential as it is the ;viral entry key allowing it to attach and enter cells to replicate. Antibodies generated by vaccination can block this interaction, preventing the virus from replicating; this is called neutralization. SARS-CoV-2 is under tremendous selective pressure, particularly for the S glycoprotein, resulting in the appearance of mutations. Recent studies have shown a significant loss of neutralization against emerging variants of concern (VOCs), such as the Alpha, Beta and Delta variants. However, the vaccine remains effective against severe cases, suggesting that vaccine protection is not solely due to neutralization. Antibodies also play a crucial role in eliminating SARS-CoV-2 infected cells through Fc-effector functions including antibody-dependent cellular cytotoxicity (ADCC). We therefore believe that individuals who developed antibodies with little to no neutralizing activity will stay protected against SARS-CoV-2 and maintain this resistance across emerging VOCs through ADCC. Our studies will help determine the humoral correlates of protection against SARS-CoV-2.