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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TLDR
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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Analysis of memory B cells identifies conserved neutralizing epitopes on the N-terminal domain of variant SARS-Cov-2 spike proteins
Zhijun Wang,Frauke Muecksch,Alice Cho,Christian Gaebler,Hans-Heinrich Hoffmann,Victor Ramos,Shuaizhou Zong,Melissa Cipolla,Briana Johnson,Fabian Schmidt,Justin DaSilva,Eva Bednarski,Tarek Ben Tanfous,Raphael Raspe,Kai-Hui Yao,Yu E. Lee,Teresia Chen,Martina Turroja,Katrina G. Milard,Juan Dizon,Anna Kaczyńska,Anna Gazumyan,Thiago Y. Oliveira,Charles M. Rice,Marina Caskey,Paul D. Bieniasz,Theodora Hatziioannou,Christopher O. Barnes,Michel C. Nussenzweig +28 more
TL;DR: In this article , Chen et al. used NTD-specific probes to capture anti-NTD memory B cells in a longitudinal cohort of infected individuals, some of whom were vaccinated.
Posted ContentDOI
Stabilizing the Closed SARS-CoV-2 Spike Trimer
Jarek Juraszek,Lucy Rutten,Sven Blokland,Pascale Bouchier,Richard Voorzaat,Tina Ritschel,Mark J. G. Bakkers,Ludovic Renault,Johannes P. M. Langedijk +8 more
TL;DR: The structure-based design of soluble S trimers is reported, with increased yields and stabilities, based on introduction of single point mutations and disulfide-bridges, and the cryo-EM structure reveals a correctly folded, predominantly closed pre-fusion conformation.
Journal ArticleDOI
SARS-CoV-2 S1 is superior to the RBD as a COVID-19 subunit vaccine antigen.
TL;DR: When immunized in mice, the S1 domain induced much higher IgG and IgA antibody levels than the receptor‐binding domain (RBD) and more efficiently neutralized SARS‐CoV‐2 when adjuvanted with alum.
Journal ArticleDOI
Evaluation of a commercially-available surrogate virus neutralization test for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2).
Emelissa J. Valcourt,Kathy Manguiat,Alyssia Robinson,Julie Chih-Yu Chen,Kristina Dimitrova,Clark S. Philipson,Lise Lamoureux,Elizabeth McLachlan,Zachary Schiffman,Michael A. Drebot,Heidi Wood +10 more
TL;DR: The sVNT provides a high-throughput screening tool prior to confirmatory PRNT testing for the evaluation of SARS-CoV-2 neutralizing antibodies, and is evaluated for sensitivity, specificity, and cross-reactivity.
Journal ArticleDOI
Mosaic RBD nanoparticles protect against challenge by diverse sarbecoviruses in animal models
Alexander A. Cohen,Neeltje van Doremalen,Allison J. Greaney,Hanne Andersen,Ankur Sharma,Tyler N. Starr,Jennifer R. Keeffe,Chengcheng Fan,Jonathan E Schulz,Priyanthi N. P. Gnanapragasam,Leesa M. Kakutani,Anthony P. West,Greg Saturday,Yu E. Lee,Han Gao,Claudia A. Jette,Mark A. Lewis,Tiong Kit Tan,Alain Townsend,Jesse D. Bloom,Vincent J. Munster,Pamela J. Bjorkman +21 more
TL;DR: Mosaic-8 RBD-nanoparticles could protect against SARS-CoV-2 variants and future sarbecovirus spillovers, and Epitope mapping demonstrated increased targeting of conserved epitopes after mosaic-8 immunization.
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