Journal
MED
Volume 3, Issue 3, Pages 188-+Publisher
CELL PRESS
DOI: 10.1016/j.medj.2022.01.004
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Funding
- Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) [W911QY-20-9-003, 20-05]
- Joint Sciences and Technology Office and Joint Program Executive Office [MCDC-16-01-002 JSTO]
- Defense Advanced Research Projects Agency (DARPA) [HR0011-18-2-0001]
- National Institutes of Health (NIH) [R01 AI157155]
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This study demonstrates that neutralizing antibodies with extended half-life and lacking Fc-mediated effector functions are highly effective for pre-exposure prophylaxis of SARS-CoV-2 infection in NHPs, supporting the clinical development of ADM03820 for COVID-19 prevention.
Background: Human 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. Methods: The 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. Findings: Passive 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. Conclusions: In 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.
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