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Open AccessJournal ArticleDOI

Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies.

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.

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Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection.

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.

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

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.
References
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Journal ArticleDOI

Fast and accurate short read alignment with Burrows–Wheeler transform

TL;DR: Burrows-Wheeler Alignment tool (BWA) is implemented, a new read alignment package that is based on backward search with Burrows–Wheeler Transform (BWT), to efficiently align short sequencing reads against a large reference sequence such as the human genome, allowing mismatches and gaps.
Journal ArticleDOI

A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3

TL;DR: It appears that the 5′ and 3′ UTRs are reservoirs for genetic variations that changes the termini of proteins during evolution of the Drosophila genus.
Journal ArticleDOI

fastp: an ultra-fast all-in-one FASTQ preprocessor.

TL;DR: Fastp is developed as an ultra‐fast FASTQ preprocessor with useful quality control and data‐filtering features that can perform quality control, adapter trimming, quality filtering, per‐read quality pruning and many other operations with a single scan of the FAST Q data.
Journal ArticleDOI

UCSF ChimeraX: Meeting modern challenges in visualization and analysis.

TL;DR: This article highlights some specific advances in the areas of visualization and usability, performance, and extensibility in ChimeraX.
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