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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Versatile, Multivalent Nanobody Cocktails Efficiently Neutralize SARS-CoV-2
Yufei Xiang,Shamkumar Nambulli,Zhengyun Xiao,Heng Liu,Zhe Sang,Paul Duprex,Dina Schneidman-Duhovny,Cheng Zhang,Yi Shi +8 more
TL;DR: This work used camelid immunization and proteomics to identify a large repertoire of highly potent neutralizing nanobodies to the SARS-CoV-2 spike (S) protein receptor-binding domain (RBD) and determined a crystal structure of such an elite neutralizing Nb in complex with RBD.
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A SARS-CoV-2 variant elicits an antibody response with a shifted immunodominance hierarchy
Allison J. Greaney,Allison J. Greaney,Tyler N. Starr,Tyler N. Starr,Rachel Eguia,Andrea N. Loes,Andrea N. Loes,Khadija Khan,Farina Karim,Sandile Cele,John E. Bowen,Jennifer Logue,Davide Corti,David Veesler,David Veesler,Helen Y. Chu,Alex Sigal,Jesse D. Bloom,Jesse D. Bloom +18 more
TL;DR: In this paper, the specificities of polyclonal antibodies produced by humans infected with early 2020 isolates versus the B.1.351 variant of concern (also known as Beta or 20H/501Y), which contains mutations in multiple key spike epitopes.
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Structural basis of a public antibody response to SARS-CoV-2
Meng Yuan,Hejun Liu,Nicholas C. Wu,Chang-Chun D Lee,Xueyong Zhu,Fangzhu Zhao,Deli Huang,Wenli Yu,Yuanzi Hua,Henry Tien,Thomas F. Rogers,Thomas F. Rogers,Elise Landais,Elise Landais,Devin Sok,Devin Sok,Joseph G. Jardine,Joseph G. Jardine,Dennis R. Burton,Ian A. Wilson +19 more
TL;DR: IGHV3-53 represents a versatile public VH in neutralizing SARS-CoV-2 antibodies, where their specific germline features and minimal affinity maturation provide important insights for vaccine design and assessing outcomes.
Journal ArticleDOI
A pathophysiological model for COVID-19: Critical importance of transepithelial sodium transport upon airway infection
TL;DR: A pathophysiological model is proposed that defines the possible role of apical sodium transport mediated by the epithelial sodium channel (ENaC) during the early phases of the infection in the airways and how it triggers innate and native immunity.
Journal ArticleDOI
Relative Ratios of Human Seasonal Coronavirus Antibodies Predict the Efficiency of Cross-Neutralization of SARS-CoV-2 Spike Binding to ACE2
Yannick Galipeau,Vinayakumar Siragam,Geneviève Laroche,Erika Marion,Matthew Greig,Michaeline McGuinty,Ronald A. Booth,Yves Durocher,Miroslava Cuperlovic-Culf,Miroslava Cuperlovic-Culf,Steffany A. L. Bennett,Angela M. Crawley,Patrick M. Giguère,Curtis Cooper,Marc-André Langlois +14 more
TL;DR: In this paper, the authors performed a cross-sectional analysis of cross-reactivity and cross-neutralization to SARS-CoV-2 antigens (S-RBD, S-trimer, N) using pre-pandemic sera from four different groups: pediatrics and adolescents, older than 70 years of age, and individuals living with HCV or HIV.
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