1. Structural insights of a highly potent pan-neutralizing SARS-CoV-2 human monoclonal antibody
- Author
-
Lorena Donnici, Rino Rappuoli, Ian A. Wilson, Matteo Conti, Hugo Mouquet, Hejun Liu, Raffaele De Francesco, Claudia Sala, Ida Paciello, Gabriel Ozorowski, Timothée Bruel, Giulia Piccini, Cyril Planchais, Jonathan L. Torres, Olivier Schwartz, Jeffrey Copps, Piero Pileri, Noemi Manganaro, Elisa Pantano, Emanuele Montomoli, Delphine Planas, Andrew B. Ward, Emanuele Andreano, The Scripps Research Institute [La Jolla, San Diego], Fondazione Toscana Gabriele Monasterio, Istituto Nazionale Genetica Molecolare [Milano] (INGM), Immunologie humorale - Humoral Immunology, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Vaccine Research Institute [Créteil, France] (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Università degli Studi di Siena = University of Siena (UNISI), Università degli Studi di Milano = University of Milan (UNIMI), This work was funded by Toscana Life Sciences, through the European Research Council advanced Grant agreement number 787552 (vAMRes), the European Union’s Horizon 2020 research and innovation program under Grant agreement no. 653316, and the Italian Ministry of Health COVID-2020-12371817 project, under collaborative agreements with The Scripps Research Institute. Work in the O.S. lab is funded by Institut Pasteur, Urgence COVID-19 Fundraising Campaign of Institut Pasteur, ANRS, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), ANR/FRM Flash Covid PROTEO-SARS-CoV-2, and IDISCOVR. This work was also funded by the Bill & Melinda Gates Foundation (OPP1170236/INV-004923)., We thank B. Anderson and H. Turner for microscope assistance, C. Bowman for computational assistance, and G.K. Hedestam and M. Corcoran for scientific discussion regarding human antibody germline genes. We thank Dr. Piet Maes from NRC UZ/KU Leuven (Leuven, Belgium) for kindly providing the Omicron live., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-20-COVI-0059,PROTEO-SARS-CoV-2,Protéomique du SARS-CoV-2(2020), and European Project: 653316,H2020,H2020-INFRAIA-2014-2015,EVAg(2015)
- Subjects
2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,medicine.drug_class ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,[SDV]Life Sciences [q-bio] ,Cell ,Antibody Affinity ,cryoelectron microscopy ,Alpha (ethology) ,Biology ,Monoclonal antibody ,Antibodies, Viral ,variants of concern ,MESH: Antibodies, Monoclonal ,MESH: Antibodies, Neutralizing ,MESH: Antibody Affinity ,Neutralization Tests ,medicine ,Potency ,Humans ,MESH: COVID-19 ,MESH: SARS-CoV-2 ,MESH: Humans ,Multidisciplinary ,SARS-CoV-2 ,monoclonal therapy ,MESH: Neutralization Tests ,Antibodies, Monoclonal ,COVID-19 ,neutralizing antibody ,Virology ,Antibodies, Neutralizing ,medicine.anatomical_structure ,Monoclonal ,MESH: Antibodies, Viral - Abstract
As the coronavirus disease 2019 (COVID-19) pandemic continues, there is a strong need for highly potent monoclonal antibodies (mAbs) that are resistant against severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) variants of concern (VoCs). Here, we evaluate the potency of a previously described mAb J08 against these variants using cell-based assays and delve into the molecular details of the binding interaction using cryo-EM. We show that mAb J08 has low nanomolar affinity against VoCs, binds high on the receptor binding domain (RBD) ridge and is therefore unaffected by most mutations, and can bind in the RBD-up and -down conformations. These findings further validate the phase II/III human clinical trial underway using mAb J08 as a monoclonal therapy.One Sentence SummaryPotent neutralizing monoclonal antibody J08 binds SARS-CoV-2 spike independent of known escape mutations.
- Published
- 2022
- Full Text
- View/download PDF