@article{b262116729724814b01cca6123d98f7c,
title = "Neutralizing Monoclonal Antibodies That Target the Spike Receptor Binding Domain Confer Fc Receptor-Independent Protection against SARS-CoV-2 Infection in Syrian Hamsters",
abstract = "The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein is the main target for neutralizing antibodies. These antibodies can be elicited through immunization or passively transferred as therapeutics in the form of convalescent-phase sera or monoclonal antibodies (MAbs). Potently neutralizing antibodies are expected to confer protection; however, it is unclear whether weakly neutralizing antibodies contribute to protection. Also, their mechanism of action in vivo is incompletely understood. Here, we demonstrate that 2B04, an antibody with an ultrapotent neutralizing activity (50% inhibitory concentration [IC50] of 0.04 mg/ml), protects hamsters against SARS-CoV-2 in a prophylactic and therapeutic infection model. Protection is associated with reduced weight loss and viral loads in nasal turbinates and lungs after challenge. MAb 2B04 also blocked aerosol transmission of the virus to naive contacts. We next examined three additional MAbs (2C02, 2C03, and 2E06), recognizing distinct epitopes within the receptor binding domain of spike protein that possess either minimal (2C02 and 2E06, IC50 . 20 mg/ml) or weak (2C03, IC50 of 5 mg/ml) virus neutralization capacity in vitro. Only 2C03 protected Syrian hamsters from weight loss and reduced lung viral load after SARS-CoV-2 infection. Finally, we demonstrated that Fc-Fc receptor interactions were not required for protection when 2B04 and 2C03 were administered prophylactically. These findings inform the mechanism of protection and support the rational development of antibody-mediated protection against SARS-CoV-2 infections.",
keywords = "COVID-19, Monoclonal antibodies, SARS-CoV-2, Syrian hamster, Transmission",
author = "Wen Su and Sia, {Sin Fun} and Schmitz, {Aaron J.} and Bricker, {Traci L.} and Starr, {Tyler N.} and Greaney, {Allison J.} and Turner, {Jackson S.} and Mohammed, {Bassem M.} and Zhuoming Liu and Choy, {Ka Tim} and Darling, {Tamarand L.} and Astha Joshi and Cheng, {Ka Man} and Wong, {Alvina Y.L.} and Harastani, {Houda H.} and Nicholls, {John M.} and Whelan, {Sean P.J.} and Bloom, {Jesse D.} and Yen, {Hui Ling} and Ellebedy, {Ali H.} and Boon, {Adrianus C.M.}",
note = "Funding Information: R01-AI118938). HKU received funding (AI151810-01) from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, USA, Theme-Based Research Scheme (T11-712/19-N) from the Research Grants Council, and HMRF Commissioned study (COVID190126) from the Food and Health Bureau, Hong Kong SAR, China. The Ellebedy laboratory was supported by NIAID grants U01AI141990 and U01AI150747, NIAID Centers of Excellence for Influenza Research, by Surveillance contracts HHSN272201400006C and HHSN272201400008C, and by NIAID Collaborative Influenza Vaccine Innovation Centers contract 75N93019C00051. Funding Information: The Boon laboratory has received unrelated funding support in sponsored research agreements from AI Therapeutics, GreenLight Biosciences Inc., and Nano Targeting & Therapy Biopharma Inc. The Boon laboratory has received funding support from AbbVie Inc., for the commercial development of SARS-CoV-2 MAb. The Ellebedy laboratory received funding under sponsored research agreements that are unrelated to the data presented in the current study from Emergent BioSolutions and from AbbVie. A.H.E. is the founder of ImmuneBio Consulting LLC. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of the funding agencies. Funding Information: We thank Susan Cook and Ken Boschert for technical support of the COVID-19 research. This study was funded by NIH contracts and grants (U01 AI151810, R01-AI139251, and Funding Information: We thank Susan Cook and Ken Boschert for technical support of the COVID-19 research. This study was funded by NIH contracts and grants (U01 AI151810, R01-AI139251, and R01-AI118938). HKU received funding (AI151810-01) from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, USA, Theme-Based Research Scheme (T11-712/19-N) from the Research Grants Council, and HMRF Commissioned study (COVID190126) from the Food and Health Bureau, Hong Kong SAR, China. The Ellebedy laboratory was supported by NIAID grants U01AI141990 and U01AI150747, NIAID Centers of Excellence for Influenza Research, by Surveillance contracts HHSN272201400006C and HHSN272201400008C, and by NIAID Collaborative Influenza Vaccine Innovation Centers contract 75N93019C00051. Publisher Copyright: Copyright {\textcopyright} 2021 Su et al.",
year = "2021",
month = oct,
day = "1",
doi = "10.1128/mBio.02395-21",
language = "English",
volume = "12",
journal = "mBio",
issn = "2161-2129",
number = "5",
}