Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants.
Yiska Weisblum,Fabian Schmidt,Fengwen Zhang,Justin DaSilva,Daniel Poston,Julio C. C. Lorenzi,Frauke Muecksch,Magdalena Rutkowska,Hans-Heinrich Hoffmann,Eleftherios Michailidis,Christian Gaebler,Marianna Agudelo,Alice Cho,Zijun Wang,Anna Gazumyan,Melissa Cipolla,Larry L. Luchsinger,Christopher D. Hillyer,Marina Caskey,Davide F. Robbiani,Davide F. Robbiani,Charles M. Rice,Michel C. Nussenzweig,Michel C. Nussenzweig,Theodora Hatziioannou,Paul D. Bieniasz,Paul D. Bieniasz +26 more
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TLDR
It is shown that functional SARS-CoV-2 S protein variants with mutations in the receptor-binding domain (RBD) and N-terminal domain that confer resistance to monoclonal antibodies or convalescent plasma can be readily selected.Abstract:
Neutralizing antibodies elicited by prior infection or vaccination are likely to be key for future protection of individuals and populations against SARS-CoV-2. Moreover, passively administered antibodies are among the most promising therapeutic and prophylactic anti-SARS-CoV-2 agents. However, the degree to which SARS-CoV-2 will adapt to evade neutralizing antibodies is unclear. Using a recombinant chimeric VSV/SARS-CoV-2 reporter virus, we show that functional SARS-CoV-2 S protein variants with mutations in the receptor-binding domain (RBD) and N-terminal domain that confer resistance to monoclonal antibodies or convalescent plasma can be readily selected. Notably, SARS-CoV-2 S variants that resist commonly elicited neutralizing antibodies are now present at low frequencies in circulating SARS-CoV-2 populations. Finally, the emergence of antibody-resistant SARS-CoV-2 variants that might limit the therapeutic usefulness of monoclonal antibodies can be mitigated by the use of antibody combinations that target distinct neutralizing epitopes.read more
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SARS-CoV-2 variants, spike mutations and immune escape.
William T. Harvey,Alessandro M Carabelli,Ben Jackson,Ravindra K. Gupta,E. Thomson,E. Thomson,Ewan M. Harrison,Ewan M. Harrison,Catherine Ludden,Richard Reeve,Andrew Rambaut,Sharon J. Peacock,David Robertson +12 more
TL;DR: A review of the literature on mutations of the SARS-CoV-2 spike protein, the primary antigen, focusing on their impacts on antigenicity and contextualizing them in the protein structure is presented in this article.
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Safety and Efficacy of Single-Dose Ad26.COV2.S Vaccine against Covid-19.
Jerald C. Sadoff,Glenda Gray,An Vandebosch,Vicky Cardenas,Georgi Shukarev,Beatriz Grinsztejn,Paul A. Goepfert,Carla Truyers,Hein Fennema,Bart Spiessens,Kim Offergeld,Gert Scheper,Kimberly L Taylor,Merlin L. Robb,John J. Treanor,Dan H. Barouch,Jeffrey J. Stoddard,Martin Ryser,Mary A. Marovich,Kathleen M. Neuzil,Lawrence Corey,Nancy Cauwenberghs,Tamzin Tanner,Karin Hardt,Javier Ruiz-Guiñazú,Mathieu Le Gars,Hanneke Schuitemaker,Johan Van Hoof,Frank Struyf,Macaya Douoguih +29 more
TL;DR: A single dose of Ad26.COV2.S protected against symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection and was effective against severe–critical disease, including hospitalization and death, in an international, randomized, double-blind, placebo-controlled, phase 3 trial.
Journal ArticleDOI
Detection of a SARS-CoV-2 variant of concern in South Africa.
Houriiyah Tegally,Eduan Wilkinson,Marta Giovanetti,Marta Giovanetti,Arash Iranzadeh,Vagner Fonseca,Vagner Fonseca,Jennifer Giandhari,Deelan Doolabh,Sureshnee Pillay,Emmanuel James San,Nokukhanya Msomi,Koleka Mlisana,Anne von Gottberg,Sibongile Walaza,Mushal Allam,Arshad Ismail,Thabo Mohale,Allison J. Glass,Susan Engelbrecht,Gert U. van Zyl,Wolfgang Preiser,Francesco Petruccione,Alex Sigal,Alex Sigal,Diana Hardie,Gert Marais,Nei yuan Hsiao,Stephen N.J. Korsman,Mary-Ann Davies,Lynn Tyers,Innocent Mudau,Denis York,Caroline Maslo,Dominique Goedhals,Shareef Abrahams,Oluwakemi Laguda-Akingba,Arghavan Alisoltani-Dehkordi,Arghavan Alisoltani-Dehkordi,Adam Godzik,Constantinos Kurt Wibmer,B.T. Sewell,José Lourenço,Luiz Carlos Junior Alcantara,Luiz Carlos Junior Alcantara,Sergei L Kosakovsky Pond,Steven Weaver,Darren P. Martin,Richard J Lessells,Richard J Lessells,Jinal N. Bhiman,Carolyn Williamson,Carolyn Williamson,Tulio de Oliveira,Tulio de Oliveira,Tulio de Oliveira +55 more
TL;DR: A newly arisen lineage of SARS-CoV-2 (designated 501Y.V2) was identified in South Africa after the first wave of the epidemic in a severely affected metropolitan area (Nelson Mandela Bay) that is located on the coast of the Eastern Cape province.
Journal ArticleDOI
SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies.
Christopher O. Barnes,Claudia A. Jette,Morgan E. Abernathy,Kim Marie A. Dam,Shannon R. Esswein,Harry B. Gristick,Andrey G. Malyutin,Naima G. Sharaf,Kathryn E. Huey-Tubman,Yu E. Lee,Davide F. Robbiani,Davide F. Robbiani,Michel C. Nussenzweig,Michel C. Nussenzweig,Anthony P. West,Pamela J. Bjorkman +15 more
TL;DR: Eight new structures of distinct COVID-19 human neutralizing antibodies 5 in complex with the SARS-CoV-2 spike trimer or RBD are solved and rules for assigning current and future human RBD-targeting antibodies into classes, evaluating avidity effects and suggesting combinations for clinical use are provided.
Journal ArticleDOI
Evolution of antibody immunity to SARS-CoV-2.
Christian Gaebler,Zijun Wang,Julio C. C. Lorenzi,Frauke Muecksch,Shlomo Finkin,Minami Tokuyama,Alice Cho,Mila Jankovic,Dennis Schaefer-Babajew,Thiago Y. Oliveira,Melissa Cipolla,Charlotte Viant,Christopher O. Barnes,Yaron Bram,Gaëlle Breton,Thomas Hagglof,Pilar Mendoza,Arlene Hurley,Martina Turroja,Kristie Gordon,Katrina G. Millard,Victor A. Ramos,Fabian Schmidt,Yiska Weisblum,Divya Jha,Michael Tankelevich,Gustavo Martinez-Delgado,Jim Yee,Roshni Patel,Juan Dizon,Cecille Unson-O'Brien,Irina Shimeliovich,Davide F. Robbiani,Zhen Zhao,Anna Gazumyan,Robert E. Schwartz,Theodora Hatziioannou,Pamela J. Bjorkman,Saurabh Mehandru,Paul D. Bieniasz,Paul D. Bieniasz,Marina Caskey,Michel C. Nussenzweig,Michel C. Nussenzweig +43 more
TL;DR: In this article, the authors report on the humoral memory response in a cohort of 87 individuals assessed at 1.3 and 6.2 months after infection with SARS-CoV-2.
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Convergent antibody responses to SARS-CoV-2 in convalescent individuals.
Davide F. Robbiani,Davide F. Robbiani,Christian Gaebler,Frauke Muecksch,Julio C. C. Lorenzi,Zijun Wang,Alice Cho,Marianna Agudelo,Christopher O. Barnes,Anna Gazumyan,Shlomo Finkin,Thomas Hagglof,Thiago Y. Oliveira,Charlotte Viant,Arlene Hurley,Hans Heinrich Hoffmann,Katrina G. Millard,Rhonda G. Kost,Melissa Cipolla,Kristie Gordon,Filippo Bianchini,Spencer T. Chen,Victor A. Ramos,Roshni Patel,Juan Dizon,Irina Shimeliovich,Pilar Mendoza,Harald Hartweger,Lilian Nogueira,Maggi Pack,Jill Horowitz,Fabian Schmidt,Yiska Weisblum,Eleftherios Michailidis,Alison W. Ashbrook,Eric Waltari,John E. Pak,Kathryn E. Huey-Tubman,Nicholas Koranda,Pauline R. Hoffman,Anthony P. West,Charles M. Rice,Theodora Hatziioannou,Pamela J. Bjorkman,Paul D. Bieniasz,Paul D. Bieniasz,Marina Caskey,Michel C. Nussenzweig,Michel C. Nussenzweig +48 more
TL;DR: Most convalescent plasma samples obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity, and rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.
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