Potent neutralizing antibodies from COVID-19 patients define multiple targets of vulnerability.
Philip J. M. Brouwer,Tom G. Caniels,Karlijn van der Straten,Jonne L. Snitselaar,Yoann Aldon,Sandhya Bangaru,Jonathan L. Torres,Nisreen M.A. Okba,Mathieu Claireaux,Gius Kerster,Arthur E. H. Bentlage,Marlies M. van Haaren,Denise Guerra,Judith A. Burger,Edith E. Schermer,Kirsten D. Verheul,Niels van der Velde,Alex van der Kooi,Jelle van Schooten,Mariëlle J. van Breemen,Tom P. L. Bijl,Kwinten Sliepen,Aafke Aartse,Aafke Aartse,Ronald Derking,Ilja Bontjer,Neeltje A. Kootstra,W. Joost Wiersinga,Gestur Vidarsson,Bart L. Haagmans,Andrew B. Ward,Godelieve J. de Bree,Rogier W. Sanders,Rogier W. Sanders,Marit J. van Gils +34 more
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It is shown that the patients had strong immune responses against the viral spike protein, a complex that binds to receptors on the host cell, and monoclonal antibodies isolated here are promising candidates for COVID-19 treatment and prevention.Abstract:
The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a large impact on global health, travel, and economy. Therefore, preventative and therapeutic measures are urgently needed. Here, we isolated monoclonal antibodies from three convalescent coronavirus disease 2019 (COVID-19) patients using a SARS-CoV-2 stabilized prefusion spike protein. These antibodies had low levels of somatic hypermutation and showed a strong enrichment in VH1-69, VH3-30-3, and VH1-24 gene usage. A subset of the antibodies was able to potently inhibit authentic SARS-CoV-2 infection at a concentration as low as 0.007 micrograms per milliliter. Competition and electron microscopy studies illustrate that the SARS-CoV-2 spike protein contains multiple distinct antigenic sites, including several receptor-binding domain (RBD) epitopes as well as non-RBD epitopes. In addition to providing guidance for vaccine design, the antibodies described here are promising candidates for COVID-19 treatment and prevention.read more
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SARS-CoV-2 Serology Status Detected by Commercialized Platforms Distinguishes Previous Infection and Vaccination Adaptive Immune Responses
Raymond T. Suhandynata,Nicholas J Bevins,Jenny Tuyet Tran,Deli Huang,Melissa A Hoffman,Kyle Lund,Michael J. Kelner,Ronald W. McLawhon,Steven L. Gonias,David Nemazee,Robert L. Fitzgerald +10 more
TL;DR: In this article, the ability of four commercial SARS-CoV-2 serology platforms to detect previous infection or vaccination were evaluated using a cohort of 53 SARS CoV 2 PCR-positive patients, 89 SARSCoV 2 vaccinated healthcare workers (Pfizer or Moderna), and 127 SARS coV 2 negative patients.
Journal ArticleDOI
From structure to sequence: Antibody discovery using cryoEM
Aleksandar Antanasijevic,Charles A. Bowman,Robert N. Kirchdoerfer,Christopher A. Cottrell,Gabriel Ozorowski,Amit A. Upadhyay,Kimberly M. Cirelli,Diane G. Carnathan,Chiamaka A. Enemuo,L.M. Sewall,Bartek Nogal,Fangzhu Zhao,Bettina Groschel,William R. Schief,Devin Sok,Guido Silvestri,Shane Crotty,Steven E. Bosinger,Andrew B. Ward +18 more
TL;DR: A hybrid structural and bioinformatic approach is presented to directly assign the heavy and light chains, identify complementarity-determining regions, and discover sequences from cryoEM density maps of serum-derived polyclonal antibodies bound to an antigen.
Journal ArticleDOI
Development of SARS-CoV2 humoral response including neutralizing antibodies is not sufficient to protect patients against fatal infection
Mathilde Choteau,Anaïs Scohy,Stéphane Messe,Mathieu Luyckx,Mélanie Dechamps,Virginie Montiel,Jean Cyr Yombi,Damien Gruson,Nisha Limaye,Thomas Michiels,Laure Dumoutier +10 more
TL;DR: In this paper , the authors characterized the antibody response in 187 COVID-19 patients, ranging from asymptomatic individuals to patients who died from SARS-CoV-2 infection, and including patients who recovered.
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Multi-Clonal Live SARS-CoV-2 In Vitro Neutralization by Antibodies Isolated from Severe COVID-19 Convalescent Donors
Michael Mor,Michal Werbner,Joel Alter,Modi Safra,Elad Chomsky,Smadar Hada-Neeman,Ksenia Polonsky,Cameron J. Nowell,Alex E. Clark,Anna Roitburd-Berman,Noam Ben-Shalom,Michal Navon,Dor Rafael,Hila Sharim,Evgeny Kiner,Eric R. Griffis,Jonathan M. Gershoni,Oren Kobiler,Sandra L Leibel,Oren Zimhony,Aaron F. Carlin,Gur Yaari,Moshe Dassau,Meital Gal-Tanamy,David Hagin,Ben A. Croker,Natalia T. Freund +26 more
TL;DR: It is demonstrated that severe COVID-19 is associated with unique BCR signatures and multi-clonal neutralizing responses that are relatively frequent in the population and the data support the use of combination antibody therapy to prevent and treat CO VID-19.
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Generation of a cost-effective cell line for support of high-throughput isolation of primary human B cells and monoclonal neutralizing antibodies.
Rachael E. Whaley,Sarah Ameny,Tanvi Arkatkar,Aaron Seese,Abigail Wall,Iram F. Khan,Joseph J. Carter,Erin M. Scherer,David J. Rawlings,Denise A. Galloway,M. Juliana McElrath,Kristen W. Cohen,Andrew T. McGuire,Andrew T. McGuire +13 more
TL;DR: It is shown that this approach can be used to isolate B cells that secrete antibodies that neutralize human papilloma virus (HPV) from participants of an HPV vaccine study.
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