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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Th1 Dominant Nucleocapsid and Spike Antigen-Specific CD4+ and CD8+ Memory T Cell Recall Induced by hAd5 S-Fusion + N-ETSD Infection of Autologous Dendritic Cells from Patients Previously Infected with SARS-CoV-2
Peter A. Sieling,Lise Zakin,Annie Shin,Brett Morimoto,Helty Adisetiyo,Hermes Garban,Philip T. Liu,Adrian Rice,Justin Taft,Roosheel S. Patel,Sofija Buta,Marta Martín-Fernández,Dusan Bogunovic,Elizabeth Gabitzsch,Jeffrey T. Safrit,Lennie Sender,Patricia Spilman,Shahrooz Rabizadeh,Kayvan Niazi,Patrick Soon-Shiong +19 more
TL;DR: It is reported that the hAd5 S-Fusion + N-ETSD vaccine is recognized by anti-sera and T cells from previously SARS-CoV-2 infected patients, and that the presence of N is vital for T-cell recall.
Journal ArticleDOI
Atomistic Simulations and In Silico Mutational Profiling of Protein Stability and Binding in the SARS-CoV-2 Spike Protein Complexes with Nanobodies: Molecular Determinants of Mutational Escape Mechanisms.
TL;DR: In this paper, the authors combine atomistic simulations with the ensemble-based mutational profiling of binding for SARS-CoV-2 S-RBD complexes to identify dynamic and binding affinity fingerprints and characterize the energetic determinants of nanobody-escaping mutations.
Journal ArticleDOI
Coronavirus Pseudotypes for All Circulating Human Coronaviruses for Quantification of Cross-Neutralizing Antibody Responses.
Alexander Thomas Sampson,Jonathan L. Heeney,Diego Cantoni,Matteo Ferrari,Maria Suau Sans,Charlotte George,Cecilia Di Genova,Martin Mayora Neto,Sebastian Einhauser,Benedikt Asbach,Ralf Wagner,Ralf Wagner,Helen Baxendale,Nigel J. Temperton,George Carnell +14 more
TL;DR: In this article, a panel of lentiviral pseudotypes bearing the spike (S) proteins for each of the seven human coronaviruses (HCoVs), generated under similar conditions optimized for high titre production allowing a high-throughput investigation of antibody neutralization breadth.
Posted ContentDOI
Cross-reactive coronavirus antibodies with diverse epitope specificities and extra-neutralization functions.
Andrea R. Shiakolas,Kevin J Kramer,Daniel Wrapp,Simone I. Richardson,Alexandra Schäfer,Steven C. Wall,Nianshuang Wang,Katarzyna Janowska,Kelsey A. Pilewski,Rohit Venkat,R Parks,Nelia P. Manamela,Nagarajan Raju,Emilee Friedman Fechter,Clinton M. Holt,Naveenchandra Suryadevara,Rita E. Chen,David R. Martinez,Rachel S. Nargi,Rachel E. Sutton,Julie E. Ledgerwood,Barney S. Graham,Michael S. Diamond,Barton F. Haynes,Priyamvada Acharya,Robert H. Carnahan,James E. Crowe,Ralph S. Baric,Lynn Morris,Jason S. McLellan,Ivelin S. Georgiev +30 more
TL;DR: In this paper, the authors applied a high-throughput sequencing method called LIBRA-seq (Linking B cell receptor to antigen specificity through sequencing) to a SARS-CoV-1 convalescent donor sample.
Journal ArticleDOI
Durable Antibody Responses in Staff at Two Long-Term Care Facilities, during and Post SARS-CoV-2 Outbreaks.
Emily N Gallichotte,Mary Nehring,Michael C. Young,Sierra Pugh,Nicole R Sexton,Emily Fitzmeyer,Kendra M Quicke,Megan Richardson,Kristy L. Pabilonia,Nicole Ehrhart,Bailey K. Fosdick,Sue VandeWoude,Gregory D. Ebel +12 more
TL;DR: In this article, the authors performed weekly surveillance testing of staff at two long-term care facilities (LTCFs) to detect presymptomatic infections and identify infected workers, which revealed a large outbreak at one of the sites.
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