Article
Author: Cook, Anthony ; Dorsey, Nicole M ; Nkolola, Joseph ; Hechenblaickner, Manuel ; Lewis, Mark G ; Hackett, Kyal ; Nonet, Genevieve H ; Earnhart, Christopher G ; Chandrashekar, Abishek ; Carnahan, Robert H ; Andersen, Hanne ; Barouch, Dan H ; Hopkins, Svetlana A ; Crowe, James E ; Collins, Laura ; Gilchuk, Pavlo ; Cobb, Ronald R ; House, Robert V ; Snow, Doris M ; Chen, Rita E ; Diamond, Michael S ; Yu, Jingyou ; VanBlargan, Laura A ; Hoppe, Brian ; Slaughter, James C ; Tomic, Milan T
BACKGROUNDHuman monoclonal antibody (mAb) treatments are promising for COVID-19 prevention or therapy. The pre-exposure prophylactic efficacy of neutralizing antibodies that are engineered with mutations to extend their persistence in human serum and the neutralizing antibody titer in serum required for protection against SARS-CoV-2 infection remain poorly characterized.METHODSThe Fc region of two neutralizing mAbs (COV2-2130 and COV2-2381) targeting non-overlapping epitopes on the receptor binding domain of SARS-CoV-2 spike protein was engineered to extend their persistence in humans and reduce interactions with Fc gamma receptors. We assessed protection by individual antibodies or a combination of the two antibodies (designated ADM03820) given prophylactically by an intravenous or intramuscular route in a non-human primate (NHP) model of SARS-CoV-2 infection.FINDINGSPassive transfer of individual mAbs or ADM03820 conferred virological protection in the NHP respiratory tract in a dose-dependent manner, and ADM03820 potently neutralized SARS-CoV-2 variants of concern in vitro. We defined a protective serum-neutralizing antibody titer and concentration in NHPs for passively transferred human antibodies that acted by direct viral neutralization.CONCLUSIONSIn summary, we demonstrate that neutralizing antibodies with extended half-life and lacking Fc-mediated effector functions are efficient for pre-exposure prophylaxis of SARS-CoV-2 infection in NHPs. These results support clinical development of ADM03820 for COVID-19 prevention.FUNDINGThis research was supported by a contract from the JPEO-CBRND (W911QY-20-9-003, 20-05); the Joint Sciences and Technology Office and Joint Program Executive Office (MCDC-16-01-002 JSTO, JPEO); a DARPA grant (HR0011-18-2-0001); an NIH grant (R01 AI157155); and the 2019 Future Insight Prize from Merck KGaA.