Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies.
Rita E. Chen,Xianwen Zhang,James Brett Case,Emma S. Winkler,Yang Liu,Laura A. VanBlargan,Jianying Liu,John M. Errico,Xuping Xie,Naveenchandra Suryadevara,Pavlo Gilchuk,Seth J. Zost,Stephen Tahan,Lindsay Droit,Jackson S. Turner,Wooseob Kim,Aaron J. Schmitz,Mahima Thapa,David Wang,Adrianus C. M. Boon,Rachel M. Presti,Jane A. O’Halloran,Alfred H.J. Kim,Parakkal Deepak,Dora Pinto,Daved H. Fremont,James E. Crowe,Davide Corti,Herbert W. Virgin,Herbert W. Virgin,Ali H. Ellebedy,Pei Yong Shi,Michael S. Diamond +32 more
TLDR
In this article, using monoclonal antibodies (mAbs), animal immune sera, human convalescent sera and human sera from recipients of the BNT162b2 mRNA vaccine, the authors report the impact on antibody neutralization of a panel of authentic SARS-CoV-2 variants including a B.1.7 isolate, chimeric strains with South African or Brazilian spike genes and isogenic recombinant viral variants.Abstract:
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global COVID-19 pandemic. Rapidly spreading SARS-CoV-2 variants may jeopardize newly introduced antibody and vaccine countermeasures. Here, using monoclonal antibodies (mAbs), animal immune sera, human convalescent sera and human sera from recipients of the BNT162b2 mRNA vaccine, we report the impact on antibody neutralization of a panel of authentic SARS-CoV-2 variants including a B.1.1.7 isolate, chimeric strains with South African or Brazilian spike genes and isogenic recombinant viral variants. Many highly neutralizing mAbs engaging the receptor-binding domain or N-terminal domain and most convalescent sera and mRNA vaccine-induced immune sera showed reduced inhibitory activity against viruses containing an E484K spike mutation. As antibodies binding to spike receptor-binding domain and N-terminal domain demonstrate diminished neutralization potency in vitro against some emerging variants, updated mAb cocktails targeting highly conserved regions, enhancement of mAb potency or adjustments to the spike sequences of vaccines may be needed to prevent loss of protection in vivo.read more
Citations
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Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection.
David S. Khoury,Deborah Cromer,Arnold Reynaldi,Timothy E. Schlub,Timothy E. Schlub,Adam K. Wheatley,Jennifer A Juno,Kanta Subbarao,Stephen J. Kent,Stephen J. Kent,Stephen J. Kent,James A. Triccas,Miles P. Davenport +12 more
TL;DR: It is shown that neutralization level is highly predictive of immune protection, and an evidence-based model of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic is provided.
Journal ArticleDOI
Mechanisms of SARS-CoV-2 entry into cells.
TL;DR: In this article, structural and cellular foundations for understanding the multistep SARS-CoV-2 entry process, including S protein synthesis, S protein structure, conformational transitions necessary for association of the spike (S) protein with ACE2, engagement of the receptor-binding domain of the S protein with ACS, proteolytic activation of S protein, endocytosis and membrane fusion are provided.
Journal ArticleDOI
The biological and clinical significance of emerging SARS-CoV-2 variants.
Kaiming Tao,Philip L Tzou,Janin Nouhin,Ravindra K. Gupta,Tulio de Oliveira,Sergei L Kosakovsky Pond,Daniela Fera,Robert W. Shafer +7 more
TL;DR: The emergence of SARS-CoV-2 variants with novel spike protein mutations that are influencing the epidemiological and clinical aspects of the COVID-19 pandemic has been witnessed as mentioned in this paper.
Journal ArticleDOI
An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies
Laura A. VanBlargan,John M. Errico,Peter Halfmann,Seth J. Zost,James E. Crowe,Lisa A. Purcell,Yoshihiro Kawaoka,Davide Corti,Daved H. Fremont,Michael S. Diamond +9 more
TL;DR: In this paper , the authors tested a panel of anti-receptor-binding domain monoclonal antibodies (mAbs) corresponding to those in clinical use by Vir Biotechnology (S309), the parent mAb of VIR-7831 (sotrovimab)), AstraZeneca (COV2-2196 and COV22130, the parentmAbs of AZD8895 and AZD1061), Regeneron (REGN10933 and REGN10987), Eli Lilly (LY-CoV555 and LY-Cov016) and Celltrion (CT-P59) for their ability to neutralize an infectious B.1.1-Omicron isolate.
Journal ArticleDOI
SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses.
Jackson S. Turner,Jane A. O’Halloran,Elizaveta Kalaidina,Wooseob Kim,Aaron J. Schmitz,Julian Q. Zhou,Tingting Lei,Mahima Thapa,Rita E. Chen,James Brett Case,Fatima Amanat,Adriana M Rauseo,Alem Haile,Xuping Xie,Michael K. Klebert,Teresa Suessen,William D. Middleton,Pei Yong Shi,Florian Krammer,Sharlene A. Teefey,Michael S. Diamond,Rachel M. Presti,Ali H. Ellebedy +22 more
TL;DR: In this article, the authors examined antigen-specific B-cell responses in peripheral blood and draining lymph nodes in 14 individuals who had received 2-doses of BNT162b2, an mRNA-based vaccine that encodes the full-length SARS-CoV-2 spike (S) gene1.
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TL;DR: This article highlights some specific advances in the areas of visualization and usability, performance, and extensibility in ChimeraX.
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