Fc-effector functions of antibodies against SARS-CoV-2: the role of accessory protein ORF8

SARS-CoV-2 is the pathogen responsible for the COVID-19 pandemic. This virus is still present in our society and despite the availability of vaccines, many cases of reinfections are observed. It is therefore important to study the adaptive immune response against SARS-CoV-2 as well as the mechanisms it uses to escape this response. Antibodies can attack viruses directly by neutralizing viral particles, but they can also help eliminate infected cells via their Fc-effector functions such as antibody-dependent cellular cytotoxicity (ADCC) or antibody-dependent cellular phagocytosis (ADCP). SARS-CoV-2 has many accessory proteins involved in host-pathogen interactions, such as ORF8 ("Open Reading Frame 8"), which is known for its inhibitory effects on host immune responses. Indeed, it was reported that this protein can reduce the number of CD16 receptors at the surface of immune cells reducing their capacity to trigger certain immune responses such as ADCC. Additionally, ORF8's presence in the plasma of infected individuals was positively associated with disease severity and mortality. Few studies have demonstrated the effects of ORF8 on Fc-effector functions such as ADCC and ADCP using authentic SARS-CoV-2 viruses. The purpose of my research is to study ORF8's effects on effector immune functions after infection with authentic SARS-CoV-2 virus. This will give us a better understanding on the virus strategies to escape the immune system.