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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SARS-CoV-2 Simulations Go Exascale to Capture Spike Opening and Reveal Cryptic Pockets Across the Proteome
Maxwell I. Zimmerman,Justin R. Porter,Michael D. Ward,Sukrit Singh,Neha Vithani,Artur Meller,Upasana L. Mallimadugula,Catherine E. Kuhn,Jonathan H. Borowsky,Rafal P. Wiewiora,Rafal P. Wiewiora,Matthew F. D. Hurley,Aoife M. Harbison,Carl A Fogarty,Joseph E. Coffland,Elisa Fadda,Vincent A. Voelz,John D. Chodera,Gregory R. Bowman +18 more
TL;DR: This simulations capture dramatic opening of the apo Spike complex, far beyond that seen experimentally, which explains and successfully predicts the existence of ‘cryptic’ epitopes in the SARS-CoV-2 proteome.
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Germinal center responses to SARS-CoV-2 mRNA vaccines in healthy and immunocompromised individuals
Katlyn Lederer,Kalpana Parvathaneni,Mark M Painter,Emily Bettini,Divyansh Agarwal,Kendall A. Lundgreen,Madison E. Weirick,Rishi R. Goel,Xiaoming Xu,Elizabeth M Drapeau,Sigrid Gouma,Allison R. Greenplate,Carole Le Coz,Carole Le Coz,Neil Romberg,Neil Romberg,Lisa Jones,Mark A. Rosen,Behdad Besharatian,Mary Kaminiski,Daniela Weiskopf,Alessandro Sette,Alessandro Sette,Scott E. Hensley,Paul Bates,E. John Wherry,Ali Naji,Vijay Bhoj,Michela Locci +28 more
TL;DR: In this paper, the immune responses to SARS-CoV-2 mRNA vaccines in lymph nodes of healthy individuals and kidney transplant (KTX) recipients were profiled through a fine-needle-aspiration-based approach.
Journal ArticleDOI
Potency of BNT162b2 and mRNA-1273 vaccine-induced neutralizing antibodies against severe acute respiratory syndrome-CoV-2 variants of concern: A systematic review of in vitro studies.
Maryam Noori,Seyed Aria Nejadghaderi,Seyed Aria Nejadghaderi,Shahnam Arshi,Kristin Carson-Chahhoud,Kristin Carson-Chahhoud,Khalil Ansarin,Ali-Asghar Kolahi,Saeid Safiri +8 more
TL;DR: A systematic review of the most recent in vitro studies evaluating the effectiveness of BNT162b2 and mRNA-1273 induced neutralizing antibodies against SARS-CoV-2 variants of concern is presented in this article.
Journal ArticleDOI
Cross-reactive coronavirus antibodies with diverse epitope specificities and Fc effector 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,Robert Parks,Nelia P. Manamela,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,Lynn Morris,Jason S. McLellan,Ivelin S. Georgiev +32 more
TL;DR: In this paper, the authors identify and characterize a panel of six monoclonal antibodies that cross-react with CoV spike (S) proteins from the highly pathogenic SARS CoV and SARS-CoV-2, and demonstrate a spectrum of reactivity against other CoV.
Journal ArticleDOI
A SARS-CoV-2 neutralizing antibody with extensive Spike binding coverage and modified for optimal therapeutic outcomes.
Yu Guo,Lisu Huang,Guangshun Zhang,Yanfeng Yao,He Zhou,Shu Shen,Bingqing Shen,Bo Li,Xin Li,Qian Zhang,Mingjie Chen,Da Chen,Jia Wu,Dan Fu,X.Q. Zeng,Mingfang Feng,Chunjiang Pi,Yuan Wang,Xingdong Zhou,Minmin Lu,Yarong Li,Yaohui Fang,Yun-Yueh Lu,Xue Hu,Shanshan Wang,W.J. Zhang,Ge Gao,Francisco Adrian,Qisheng Wang,Feng Yu,Yun Peng,Alexander G. Gabibov,Juan Min,Yuhui Wang,Heyu Huang,Alexey Stepanov,Wei Zhang,Yan Cai,Junwei Liu,Zhiming Yuan,Chen Zhang,Zhiyong Lou,Fei Deng,Hongkai Zhang,Chao Shan,Liang Schweizer,Kun Sun,Zihe Rao +47 more
TL;DR: Zhang et al. as mentioned in this paper identified potent antibodies binding to SARS-CoV-2 Spike protein from COVID-19 convalescent patients, and P4A1 was subsequently engineered to reduce the potential risk for Antibody-Dependent Enhancement of infection and to extend its half-life.
References
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Journal ArticleDOI
UCSF Chimera--a visualization system for exploratory research and analysis.
Eric F. Pettersen,Thomas D. Goddard,Conrad C. Huang,Gregory S. Couch,Daniel M. Greenblatt,Elaine C. Meng,Thomas E. Ferrin +6 more
TL;DR: Two unusual extensions are presented: Multiscale, which adds the ability to visualize large‐scale molecular assemblies such as viral coats, and Collaboratory, which allows researchers to share a Chimera session interactively despite being at separate locales.
Journal ArticleDOI
Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study
Nanshan Chen,Min Zhou,Xuan Dong,Jie-Ming Qu,Fengyun Gong,Yang Han,Yang Qiu,Jingli Wang,Ying Liu,Yuan Wei,Jia'an Xia,Ting Yu,Xinxin Zhang,Li Zhang +13 more
TL;DR: Characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia, and further investigation is needed to explore the applicability of the Mu LBSTA scores in predicting the risk of mortality in 2019-nCoV infection.
Journal ArticleDOI
An interactive web-based dashboard to track COVID-19 in real time.
TL;DR: The outbreak of the 2019 novel coronavirus disease (COVID-19) has induced a considerable degree of fear, emotional stress and anxiety among individuals around the world.
Journal ArticleDOI
Enzymatic assembly of DNA molecules up to several hundred kilobases
Daniel G. Gibson,Lei Young,Ray-Yuan Chuang,J. Craig Venter,Clyde A. Hutchison,Hamilton O. Smith +5 more
TL;DR: An isothermal, single-reaction method for assembling multiple overlapping DNA molecules by the concerted action of a 5′ exonuclease, a DNA polymerase and a DNA ligase is described.
Journal ArticleDOI
Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation.
Daniel Wrapp,Nianshuang Wang,Kizzmekia S. Corbett,Jory A. Goldsmith,Ching-Lin Hsieh,Olubukola M. Abiona,Barney S. Graham,Jason S. McLellan +7 more
TL;DR: The authors show that this protein binds at least 10 times more tightly than the corresponding spike protein of severe acute respiratory syndrome (SARS)–CoV to their common host cell receptor, and test several published SARS-CoV RBD-specific monoclonal antibodies found that they do not have appreciable binding to 2019-nCoV S, suggesting that antibody cross-reactivity may be limited between the two RBDs.
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