Antibody cocktail to SARS-CoV-2 spike protein prevents rapid mutational escape seen with individual antibodies.
Alina Baum,Benjamin O. Fulton,Elzbieta Wloga,Richard Copin,Kristen E. Pascal,Vincenzo Russo,Stephanie Giordano,Kathryn Lanza,Nicole Negron,Min Ni,Yi Wei,Gurinder S. Atwal,Andrew J. Murphy,Neil Stahl,George D. Yancopoulos,Christos A. Kyratsous +15 more
TLDR
This work investigated the development of resistance against four antibodies to the spike protein that potently neutralize SARS-CoV-2, individually as well as when combined into cocktails.Abstract:
Antibodies targeting the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) present a promising approach to combat the coronavirus disease 2019 (COVID-19) pandemic; however, concerns remain that mutations can yield antibody resistance. We investigated the development of resistance against four antibodies to the spike protein that potently neutralize SARS-CoV-2, individually as well as when combined into cocktails. These antibodies remain effective against spike variants that have arisen in the human population. However, novel spike mutants rapidly appeared after in vitro passaging in the presence of individual antibodies, resulting in loss of neutralization; such escape also occurred with combinations of antibodies binding diverse but overlapping regions of the spike protein. Escape mutants were not generated after treatment with a noncompeting antibody cocktail.read more
Citations
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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.
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
REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19.
David M. Weinreich,Sumathi Sivapalasingam,Thomas Norton,Shazia Ali,Haitao Gao,Rafia Bhore,Bret J Musser,Yuhwen Soo,Diana Rofail,Joseph Im,Christina Perry,Cynthia Pan,Romana Hosain,Adnan Mahmood,John D. Davis,Kenneth C. Turner,Andrea T. Hooper,Jennifer D. Hamilton,Alina Baum,Christos A. Kyratsous,Yunji Kim,Amanda Cook,Wendy Kampman,Anita Kohli,Yessica Sachdeva,Ximena Graber,Bari Kowal,Thomas DiCioccio,Neil Stahl,Leah Lipsich,Ned Braunstein,Gary Herman,George D. Yancopoulos +32 more
TL;DR: In this interim analysis, the REGN-COV2 antibody cocktail reduced viral load, with a greater effect in patients whose immune response had not yet been initiated or who had a high viral load at baseline.
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
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.
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