Fc-engineered antibody therapeutics with improved anti-SARS-CoV-2 efficacy.
Nature
; 599(7885): 465-470, 2021 11.
Article
in English
| MEDLINE | ID: covidwho-1428880
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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Immunoglobulin Fc Fragments
/
SARS-CoV-2
/
COVID-19
/
COVID-19 Drug Treatment
/
Antibodies, Monoclonal
Type of study:
Experimental Studies
/
Prognostic study
Limits:
Animals
/
Female
/
Humans
/
Male
Language:
English
Journal:
Nature
Year:
2021
Document Type:
Article
Affiliation country:
S41586-021-04017-w
Similar
MEDLINE
...
LILACS
LIS