|Fc-engineered antibody therapeutics with improved anti-SARS-CoV-2 efficacy.
|Year of Publication
|Yamin R, Jones AT, Hoffmann H-H, Schäfer A, Kao KS, Francis RL, Sheahan TP, Baric RS, Rice CM, Ravetch JV, Bournazos S
|2021 Sep 21
Monoclonal antibodies (mAbs) with neutralizing activity against SARS-CoV-2 have demonstrated clinical benefit in cases of mild to moderate SARS-CoV-2 infection, substantially reducing the risk for hospitalization and severe disease1-4. Treatment generally requires the administration of high doses of these mAbs with limited efficacy in preventing disease complications or mortality among hospitalized COVID-19 patients5. Here we report the development and evaluation of Fc-optimized anti-SARS-CoV-2 mAbs with superior potency to prevent or treat COVID-19 disease. In several animal models of COVID-19 disease6,7, we demonstrate that selective engagement of activating FcγRs results in improved efficacy in both preventing and treating disease-induced weight loss and mortality, significantly reducing the dose required to confer full protection upon SARS-CoV-2 challenge and treatment of pre-infected animals. Our results highlight the importance of FcγR pathways in driving antibody-mediated antiviral immunity, while excluding any pathogenic or disease-enhancing effects of FcγR engagement of anti-SARS-CoV-2 antibodies upon infection. These findings have important implications for the development of Fc-engineered mAbs with optimal Fc effector function and improved clinical efficacy against COVID-19 disease.
|R01 AI137276 / AI / NIAID NIH HHS / United States
R01 AI145870 / AI / NIAID NIH HHS / United States
R01 AI157155 / AI / NIAID NIH HHS / United States
U19 AI111825 / AI / NIAID NIH HHS / United States
Submitted by bel2021 on October 20, 2021 - 2:06pm