A combination of two human neutralizing antibodies prevents SARS-CoV-2 infection in cynomolgus macaques.

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

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.

FUNDING

This 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.

Informations de copyright

© 2022 Elsevier Inc.

Déclaration de conflit d'intérêts

R.R.C., R.V.H., D.M.S., M.H., B.H., L.C., G.H.N., M.T.T., and K.H. are employees of Ology Bioservices. C.G.E. and N.M.D. are employees of the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense for the US Department of Defense (JPEO-CBRND). S.A.H. is an employee of Logistics Management Institute (LMI), performing technical contract support for JPEO-CBRND. J.E.C. has served as a consultant for Luna Innovations, is a member of the scientific advisory board of Meissa Vaccines, and is founder of IDBiologics. The Crowe laboratory at Vanderbilt University Medical Center has received sponsored research agreements from Takeda, IDBiologics, and AstraZeneca. Vanderbilt University has applied for patents related to antibodies studied in this paper. M.S.D. is a consultant for InBios, Vir Biotechnology, Senda Biosciences, and Carnival Corporation and is on the scientific advisory boards of Moderna and Immunome. The laboratory of M.S.D. has received funding support in sponsored research agreements from Moderna, Vir Biotechnology, Kaleido, and Emergent BioSolutions.