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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Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review.
W. Joost Wiersinga,Andrew Rhodes,Allen C. Cheng,Sharon J. Peacock,Sharon J. Peacock,Hallie C. Prescott +5 more
TL;DR: This review discusses current evidence regarding the pathophysiology, transmission, diagnosis, and management of COVID-19, the novel severe acute respiratory syndrome coronavirus 2 pandemic that has caused a worldwide sudden and substantial increase in hospitalizations for pneumonia with multiorgan disease.
Journal ArticleDOI
Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7.
Pengfei Wang,Manoj S. Nair,Lihong Liu,Sho Iketani,Sho Iketani,Yang Luo,Yicheng Guo,Maple Wang,Jian Yu,Baoshan Zhang,Peter D. Kwong,Peter D. Kwong,Barney S. Graham,John R. Mascola,Jennifer Y Chang,Jennifer Y Chang,Michael T. Yin,Michael T. Yin,Magdalena E. Sobieszczyk,Magdalena E. Sobieszczyk,Christos A. Kyratsous,Lawrence Shapiro,Lawrence Shapiro,Zizhang Sheng,Yaoxing Huang,David D. Ho,David D. Ho +26 more
TL;DR: In this paper, the authors show that B.1.7 is refractory to neutralization by most monoclonal antibodies against the N-terminal domain of the spike protein and is relatively resistant to a few monoclanal antibody against the receptor-binding domain.
Journal ArticleDOI
Deep Mutational Scanning of SARS-CoV-2 Receptor Binding Domain Reveals Constraints on Folding and ACE2 Binding.
Tyler N. Starr,Allison J. Greaney,Allison J. Greaney,Sarah K Hilton,Sarah K Hilton,Daniel Ellis,Katharine H.D. Crawford,Katharine H.D. Crawford,Adam S. Dingens,Mary Jane Navarro,John E. Bowen,M. Alejandra Tortorici,Alexandra C. Walls,Neil P. King,David Veesler,Jesse D. Bloom,Jesse D. Bloom,Jesse D. Bloom +17 more
TL;DR: It is found that a substantial number of mutations to the RBD are well tolerated or even enhance ACE2 binding, including at ACE2 interface residues that vary across SARS-related coronaviruses.
Journal ArticleDOI
COVID-19 vaccine BNT162b1 elicits human antibody and T H 1 T cell responses.
Ugur Sahin,Alexander Muik,Evelyna Derhovanessian,Isabel Vogler,Lena M. Kranz,Mathias Vormehr,Alina Baum,Kristen E. Pascal,Jasmin Quandt,Daniel Maurus,Sebastian Brachtendorf,Verena Lörks,Julian Sikorski,Rolf Hilker,Dirk Becker,Ann Kathrin Eller,Jan Grützner,Carsten Boesler,Corinna Rosenbaum,Marie Cristine Kühnle,Ulrich Luxemburger,Alexandra Kemmer-Brück,David J. Langer,Martin Bexon,Stefanie Bolte,Katalin Karikó,Tania Palanche,Boris Fischer,Armin Schultz,Pei Yong Shi,Camila R. Fontes-Garfias,John L. Perez,Kena A. Swanson,Jakob Loschko,Ingrid L. Scully,Mark Cutler,Warren Kalina,Christos A. Kyratsous,David A. Cooper,Philip R. Dormitzer,Kathrin U. Jansen,Özlem Türeci +41 more
TL;DR: The robust RBD-specific antibody, T cell and favourable cytokine responses induced by the BNT162b1 mRNA vaccine suggest that it has the potential to protect against COVID-19 through multiple beneficial mechanisms.
Journal ArticleDOI
Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike.
Lihong Liu,Pengfei Wang,Manoj S. Nair,Jian Yu,Micah Rapp,Qian Wang,Yang Luo,Jasper Fuk-Woo Chan,Jasper Fuk-Woo Chan,Vincent Sahi,Amir Figueroa,Xinzheng V. Guo,Gabriele Cerutti,Jude Bimela,Jason Gorman,Tongqing Zhou,Zhiwei Chen,Zhiwei Chen,Kwok-Yung Yuen,Kwok-Yung Yuen,Peter D. Kwong,Peter D. Kwong,Joseph Sodroski,Michael T. Yin,Zizhang Sheng,Zizhang Sheng,Yaoxing Huang,Lawrence Shapiro,Lawrence Shapiro,David D. Ho +29 more
TL;DR: A diverse collection of potent neutralizing antibodies against the SARS-CoV-2 spike protein have been isolated from five patients with severe COVID-19 and high serum neutralization titres, suggesting both of these regions at the top of the viral spike are immunogenic.
References
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TL;DR: The vision for this technique is to provide a straightforward manner in which users can proceed from raw data to a reliable 3D reconstruction through a pipeline that both facilitates management of the processing steps and makes the results at each step more transparent.
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