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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Comparative molecular dynamics study of the receptor-binding domains in SARS-CoV-2 and SARS-CoV and the effects of mutations on the binding affinity.
TL;DR: A computational comparison of the receptor-binding domains (RBDs) on the spike proteins of severe respiratory syndrome coronavirus‐2 and SARS-CoV in free forms and as complexes with angiotensin-converting enzyme 2 (ACE2) as their receptor in humans found F456 and W436 emerge as two key residues governing the stability and affinity of the spike protein for its ACE2 receptor.
Posted ContentDOI
Site-specific steric control of SARS-CoV-2 spike glycosylation
Joel D. Allen,Himanshi Chawla,Firdaus Samsudin,Lorena Zuzic,Lorena Zuzic,Aishwary Tukaram Shivgan,Aishwary Tukaram Shivgan,Yasunori Watanabe,Wan-ting He,Sean Callaghan,Ge Song,Peter Yong,Philip J. M. Brouwer,Yutong Song,Yongfei Cai,Helen M. E. Duyvesteyn,Tomas Malinauskas,Joeri Kint,Paco Pino,Maria J Wurm,Martin Frank,Bing Chen,Bing Chen,David I. Stuart,Rogier W. Sanders,Rogier W. Sanders,Raiees Andrabi,Dennis R. Burton,Sai Li,Peter J. Bond,Peter J. Bond,Max Crispin +31 more
TL;DR: In this article, the authors investigate the glycosylation of recombinant SARS-CoV-2 spike proteins from five different laboratories and compare them against infectious virus S protein, finding patterns which are conserved across all samples and this can be associated with site-specific stalling of glycan maturation.
Journal ArticleDOI
Convalescent Plasma-Mediated Resolution of COVID-19 in a Patient with Humoral Immunodeficiency
Kazuhito Honjo,Ronnie M. Russell,Ran Li,Weimin Liu,Regina Stoltz,Edlue M. Tabengwa,Yutao Hua,Lynn Prichard,Ashton Kornbrust,Sarah Sterrett,Marisa B. Marques,Jose L. Lima,Chris M. Lough,Todd P McCarty,Thomas J. Ketas,Theodora Hatziioannou,Paul D. Bieniasz,Paul D. Bieniasz,David T. Redden,John P. Moore,Paul A. Goepfert,Sonya L. Heath,Beatrice H. Hahn,Randall S. Davis +23 more
TL;DR: The beneficial effects of CP are reported in a severely ill COVID-19 patient with prolonged pneumonia and advanced chronic lymphocytic leukemia, who was unable to generate an antiviral antibody response of her own.
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The SARS-CoV-2 Delta variant is poised to acquire complete resistance to wild-type spike vaccines
Yafei Liu,Noriko Arase,Jun-ichi Kishikawa,Mika Hirose,Songling Li,Asa Tada,Sumiko Matsuoka,Akemi Arakawa,Kanako Akamatsu,Chikako Ono,Hui Jin,Kazuki Kishida,Wataru Nakai,Masako Kohyama,Atsushi Nakagawa,Yoshiaki Yamagishi,Hironori Nakagami,Atsushi Kumanogoh,Yoshiharu Matsuura,Daron M. Standley,Takayuki Kato,Masato Okada,Manabu Fujimoto,Hisashi Arase +23 more
TL;DR: In this paper, the authors found that the Delta variant completely escaped from anti-N-terminal domain (NTD) neutralizing antibodies, while increasing responsiveness to anti-NTD infectivity-enhancing antibodies.
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Four SARS-CoV-2 vaccines induce quantitatively different antibody responses against SARS-CoV-2 variants
Marit J. van Gils,A.H. Ayesha Lavell,Karlijn van der Straten,Brent Appelman,Ilja Bontjer,Meliawatti Poniman,Judith A. Burger,Melissa Oomen,Joey H. Bouhuijs,Lonneke A. van Vught,Marleen A. Slim,Michiel Schinkel,Elke Wynberg,Hugo D.G. van Willigen,Marloes Grobben,Kadija Tejjani,Jonne L. Snitselaar,Tom G. Caniels,Alexander P.J. Vlaar,Maria Prins,Menno D. de Jong,Godelieve J. de Bree,Godelieve J. de Bree,Jonne J. Sikkens,Marije K. Bomers,Marije K. Bomers,Rogier W. Sanders +26 more
TL;DR: In this paper, a head-to-head comparison of the ability of sera from individuals vaccinated with either one of four vaccines (BNT162b2, mRNA-1273, AZD1222 or Ad26.COV2.S) to recognize and neutralize the four SARS-CoV-2 variants of concern (VOCs; Alpha, Beta, Gamma and Delta).
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