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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Journal ArticleDOI
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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Journal ArticleDOI
Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex.
Devin Sok,Marit J. van Gils,Matthias Pauthner,Jean-Philippe Julien,Karen L. Saye-Francisco,Jessica Hsueh,Bryan Briney,Jeong Hyun Lee,Khoa Le,Peter Lee,Yuanzi Hua,Michael S. Seaman,John P. Moore,Andrew B. Ward,Ian A. Wilson,Rogier W. Sanders,Rogier W. Sanders,Dennis R. Burton +17 more
TL;DR: The use of a recombinant HIV envelope trimer as an affinity reagent to isolate quaternary-dependent bnAbs from the peripheral blood mononuclear cells of a chronically infected donor highlights the utility of BG505 SOSIP and reveals a mosaic of antibody responses against the trimer apex within a clonal family.
Journal ArticleDOI
Challenges of convalescent plasma infusion therapy in Middle East respiratory coronavirus infection: a single centre experience
Jae-Hoon Ko,Hyeri Seok,Sun Young Cho,Young Eun Ha,Jin Yang Baek,So Hyun Kim,Yae Jean Kim,Jinkyeong Park,Chi Ryang Chung,Eun Suk Kang,Duck Cho,Marcel A. Müller,Christian Drosten,Cheol-In Kang,Doo Ryeon Chung,Jae-Hoon Song,Kyong Ran Peck +16 more
TL;DR: For effective CP infusion in MERS, donor plasma with a neutralization activity of a PRNT titre ≥1:80 should be used and ELISA IgG could substitute for the neutralization test in resource-limited situations.
Journal ArticleDOI
Identification of human neutralizing antibodies against MERS-CoV and their role in virus adaptive evolution
Xianchun Tang,Sudhakar Agnihothram,Yongjun Jiao,Jeremy Stanhope,Rachel L. Graham,Eric C. Peterson,Yuval Avnir,Aimee St. Clair Tallarico,Jared Sheehan,Quan Zhu,Ralph S. Baric,Wayne A. Marasco +11 more
TL;DR: A well-characterized nonimmune human Ab-phage library and a panning strategy with proteoliposomes and cells are used to identify seven human nAbs against the receptor-binding domain (RBD) of the MERS-CoV Spike protein.
Book ChapterDOI
Structure and function of respiratory syncytial virus surface glycoproteins.
TL;DR: The structure and function of the RSV surface glycoproteins are reviewed, including recent X-ray crystallographic data of the F glycoprotein in its pre- and postfusion conformations, and how this information informs antigen selection and vaccine development is discussed.
Journal ArticleDOI
A public antibody lineage that potently inhibits malaria infection through dual binding to the circumsporozoite protein
Joshua Tan,Joshua Tan,Brandon K. Sack,David Oyen,Isabelle Zenklusen,Isabelle Zenklusen,Luca Piccoli,Sonia Barbieri,Mathilde Foglierini,Mathilde Foglierini,Chiara Silacci Fregni,Jessica Marcandalli,Said Jongo,Salim Abdulla,Laurent Perez,Giampietro Corradin,Luca Varani,Federica Sallusto,Federica Sallusto,Betty Kim Lee Sim,Stephen L. Hoffman,Stefan H. I. Kappe,Claudia Daubenberger,Claudia Daubenberger,Ian A. Wilson,Antonio Lanzavecchia,Antonio Lanzavecchia +26 more
TL;DR: This study isolated IgM and IgG monoclonal antibodies from Tanzanian volunteers who were immunized with repeated injection of Sanaria PfSPZ Vaccine and who were found to be protected from controlled human malaria infection with infectious homologous PfSPzs.
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