Abstract
Monoclonal antibodies with neutralizing activity against SARS-CoV-2 have demonstrated clinical benefits in cases of mild-to-moderate SARS-CoV-2 infection, substantially reducing the risk for hospitalization and severe disease 1-4 . Treatment generally requires the administration of high doses of these monoclonal antibodies and has limited efficacy in preventing disease complications or mortality among hospitalized patients with COVID-19 5 . Here we report the development and evaluation of anti-SARS-CoV-2 monoclonal antibodies with optimized Fc domains that show superior potency for prevention or treatment of COVID-19. Using several animal disease models of COVID-19 6,7 , we demonstrate that selective engagement of activating Fcγ receptors results in improved efficacy in both preventing and treating disease-induced weight loss and mortality, significantly reducing the dose required to confer full protection against SARS-CoV-2 challenge and for treatment of pre-infected animals. Our results highlight the importance of Fcγ receptor pathways in driving antibody-mediated antiviral immunity and exclude the possibility of pathogenic or disease-enhancing effects of Fcγ receptor engagement of anti-SARS-CoV-2 antibodies upon infection. These findings have important implications for the development of Fc-engineered monoclonal antibodies with optimal Fc-effector function and improved clinical efficacy against COVID-19 disease.
【초록키워드】 COVID-19, Treatment, SARS-CoV-2, Efficacy, High dose, Mortality, Hospitalization, antibody, SARS-COV-2 infection, monoclonal antibody, Infection, risk, hospitalized patients, monoclonal antibodies, anti-SARS-CoV-2, Fcγ receptor, COVID-19 disease, anti-SARS-CoV-2 antibodies, Neutralizing activity, anti-SARS-CoV-2 antibody, pathway, Complication, Disease model, receptor, antiviral immunity, Clinical efficacy, administration, dose, severe disease, Mild-to-moderate, weight loss, treatment of COVID-19, clinical benefits, domain, clinical benefit, pathogenic, selective, driving, receptor engagement, Effect, implication, highlight, significantly, required, hospitalized patient, reducing, demonstrated, activating, preventing disease, with COVID-19, 【제목키워드】 Efficacy, anti-SARS-CoV-2, Antibody therapeutics,