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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Cross-species tropism and antigenic landscapes of circulating SARS-CoV-2 variants
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TL;DR: In this article , the authors investigated 153 RBD mutants and 11 globally circulating variants of concern (VOCs) and variants of interest (VOIs) (including Omicron) for their antigenic changes and cross-species tropism in cells expressing 18 ACE2 orthologs.
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Mosaic RBD nanoparticles protect against multiple sarbecovirus challenges in animal models
Alexander A. Cohen,Neeltje van Doremalen,Allison J. Greaney,Hanne Andersen,Ankur Sharma,Tyler N. Starr,Jennifer R. Keeffe,Chen-Hua 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.
Posted ContentDOI
Disease-associated antibody phenotypes and probabilistic seroprevalence estimates during the emergence of SARS-CoV-2
Xaquin Castro Dopico,Leo Hanke,Daniel J. Sheward,Sandra Muschiol,Soo Aleman,Nastasiya F. Grinberg,Murray Christian,Monika Adori,Laura Perez Vidakovics,Kim Chang Il,Sharesta Khoenkhoen,Pradeepa Pushparaj,Ainhoa Moliner Morro,Marco Mandolesi,Marcus Ahl,Mattias Forsell,Jonathan M. Coquet,Martin Corcoran,Joanna Rorbach,Joanna Rorbach,Joakim Dillner,Gordana Bogdanovic,Gerald M. McInerney,Tobias Allander,Tobias Allander,Ben Murrell,Chris Wallace,Jan Albert,Jan Albert,Gunilla B. Karlsson Hedestam +29 more
TL;DR: In this article, the authors developed highly sensitive and specific trimeric spike (S)-based antibody tests, and reported IgM, IgG and IgA responses to SARS-CoV-2 in COVID-19 patients (n=105) representing different categories of disease severity.
Journal ArticleDOI
AbAdapt: an adaptive approach to predicting antibody–antigen complex structures from sequence
Ana Davila,Zichang Xu,Songling Li,John Rozewicki,Jan Wilamowski,Sergei Kotelnikov,Dima Kozakov,Shunsuke Teraguchi,Daron M. Standley +8 more
TL;DR: AbAdapt as discussed by the authors is a web-server that accepts antibody and antigen sequences, models their 3D structures, predicts epitope and paratope, and then docks the modeled structures using two established docking engines.
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Immunoglobulin germline gene polymorphisms influence the function of SARS-CoV-2 neutralizing antibodies
Pradeepa Pushparaj,Andrea Nicoletto,Daniel J. Sheward,Hrishikesh Das,Xaquin Castro Dopico,Laura Perez Vidakovics,Leo Hanke,Mark Chernyshev,Sanjana Narang,Sungyong Kim,Julian Fischbach,Simon Ekström,Gerald M. McInerney,B. Martin Hällberg,Ben Murrell,Martin Corcoran,Gunilla B. Karlsson Hedestam +16 more
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