Fc-engineered antibody therapeutics with improved anti-SARS-CoV-2 efficacy.
| Publication Type | Academic Article |
| Authors | Yamin R, Jones A, Hoffmann H, Schäfer A, Kao K, Francis R, Sheahan T, Baric R, Rice C, Ravetch J, Bournazos S |
| Journal | Nature |
| Volume | 599 |
| Issue | 7885 |
| Pagination | 465-470 |
| Date Published | 09/21/2021 |
| ISSN | 1476-4687 |
| Keywords | Antibodies, Monoclonal, COVID-19, Immunoglobulin Fc Fragments, SARS-CoV-2, COVID-19 Drug Treatment |
| 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 disease1-4. 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-195. 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-196,7, 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. |
| DOI | 10.1038/s41586-021-04017-w |
| PubMed ID | 34547765 |
| PubMed Central ID | PMC9038156 |