Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies

Nature, Journal Year: 2021, Volume and Issue: 602(7898), P. 657 - 663

Published: Dec. 23, 2021

The SARS-CoV-2 B.1.1.529 (Omicron) variant contains 15 mutations of the receptor-binding domain (RBD). How Omicron evades RBD-targeted neutralizing antibodies requires immediate investigation. Here we use high-throughput yeast display screening1,2 to determine profiles RBD escaping for 247 human anti-RBD and show that can be classified by unsupervised clustering into six epitope groups (A-F)-a grouping is highly concordant with knowledge-based structural classifications3-5. Various single impair different groups. Specifically, in A-D, epitopes which overlap ACE2-binding motif, are largely escaped K417N, G446S, E484A Q493R. Antibodies group E (for example, S309)6 F CR3022)7, often exhibit broad sarbecovirus activity, less affected Omicron, but a subset still G339D, N440K S371L. Furthermore, pseudovirus neutralization showed sustained could also escaped, owing multiple synergetic on their epitopes. In total, over 85% tested were Omicron. With regard neutralizing-antibody-based drugs, potency LY-CoV016, LY-CoV555, REGN10933, REGN10987, AZD1061, AZD8895 BRII-196 was greatly undermined whereas VIR-7831 DXP-604 functioned at reduced efficacy. Together, our data suggest infection would result considerable humoral immune evasion, targeting conserved region will remain most effective. Our results inform development antibody-based drugs vaccines against future variants.

Language: Английский

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BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection

Nature, Journal Year: 2022, Volume and Issue: 608(7923), P. 593 - 602

Published: June 17, 2022

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility than the BA.2 lineage 1 . The receptor binding immune-evasion capability of these recently emerged variants require immediate investigation. Here, coupled with structural comparisons spike proteins, we show that (BA.4 are hereafter referred collectively to as BA.4/BA.5) similar affinities for angiotensin-converting enzyme (ACE2) receptor. Of note, BA.2.12.1 BA.4/BA.5 display increased evasion neutralizing antibodies compared against plasma from triple-vaccinated individuals or who developed a BA.1 infection after vaccination. To delineate underlying antibody-evasion mechanism, determined escape mutation profiles , epitope distribution 3 Omicron-neutralization efficiency 1,640 directed receptor-binding domain viral protein, including 614 isolated people had recovered infection. vaccination predominantly recalls humoral immune memory ancestral (hereafter wild-type (WT)) SARS-CoV-2 protein. resulting elicited could neutralize both WT enriched on epitopes do not bind ACE2. However, most cross-reactive evaded by mutants L452Q, L452R F486V. can also induce new clones BA.1-specific potently BA.1. Nevertheless, largely owing D405N F486V mutations, react weakly pre-Omicron variants, exhibiting narrow neutralization breadths. therapeutic bebtelovimab 4 cilgavimab 5 effectively BA.4/BA.5, whereas S371F, R408S mutations undermine broadly sarbecovirus-neutralizing antibodies. Together, our results indicate may evolve evade immunity infection, suggesting BA.1-derived vaccine boosters achieve broad-spectrum protection variants.

Language: Английский

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Alarming antibody evasion properties of rising SARS-CoV-2 BQ and XBB subvariants

Cell, Journal Year: 2022, Volume and Issue: 186(2), P. 279 - 286.e8

Published: Dec. 14, 2022

The BQ and XBB subvariants of SARS-CoV-2 Omicron are now rapidly expanding, possibly due to altered antibody evasion properties deriving from their additional spike mutations. Here, we report that neutralization BQ.1, BQ.1.1, XBB, XBB.1 by sera vaccinees infected persons was markedly impaired, including individuals boosted with a WA1/BA.5 bivalent mRNA vaccine. Titers against were lower 13- 81-fold 66- 155-fold, respectively, far beyond what had been observed date. Monoclonal antibodies capable neutralizing the original variant largely inactive these new subvariants, responsible individual mutations identified. These found have similar ACE2-binding affinities as predecessors. Together, our findings indicate present serious threats current COVID-19 vaccines, render all authorized antibodies, may gained dominance in population because advantage evading antibodies.

Language: Английский

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SARS-CoV-2 Omicron variant: recent progress and future perspectives

Signal Transduction and Targeted Therapy, Journal Year: 2022, Volume and Issue: 7(1)

Published: April 28, 2022

Abstract Since the outbreak of coronavirus disease 2019 (COVID-19) pandemic, there have been a few variants severe acute respiratory syndrome 2 (SARS-CoV-2), one which is Omicron variant (B.1.1.529). The most mutated SARS-CoV-2 variant, and its high transmissibility immune evasion ability raised global concerns. Owing to enhanced transmissibility, has rapidly replaced Delta as dominant in several regions. However, recent studies shown that exhibits reduced pathogenicity due altered cell tropism. In addition, significant resistance neutralizing activity vaccines, convalescent serum, antibody therapies. present review, advances molecular clinical characteristics infectivity, pathogenicity, was summarized, potential therapeutic applications response infection were discussed. Furthermore, we highlighted future waves strategies end pandemic.

Language: Английский

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Receptor binding and complex structures of human ACE2 to spike RBD from omicron and delta SARS-CoV-2

Cell, Journal Year: 2022, Volume and Issue: 185(4), P. 630 - 640.e10

Published: Jan. 6, 2022

Language: Английский

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Defining variant-resistant epitopes targeted by SARS-CoV-2 antibodies: A global consortium study

Science, Journal Year: 2021, Volume and Issue: 374(6566), P. 472 - 478

Published: Sept. 23, 2021

Community of antibodies against COVID-19 The severe acute respiratory syndrome coronavirus 2 spike protein is the basis many vaccines and a primary target neutralizing after infection. Coronavirus Immunotherapeutic Consortium (CoVIC), comprising 56 partners across world, has analyzed panel 269 monoclonal (mAbs) and, on competition profiles, sorted 186 mAbs that receptor binding domain into seven communities. Hastie et al . went to structurally analyze representative antibody used pseudovirus neutralization assays study effect mutations function, including combinations found in certain variants concern. These results are important guide both treatment prevention efforts. —VV

Language: Английский

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Monoclonal antibodies for COVID-19 therapy and SARS-CoV-2 detection

Journal of Biomedical Science, Journal Year: 2022, Volume and Issue: 29(1)

Published: Jan. 4, 2022

The coronavirus disease 2019 (COVID-19) pandemic is an exceptional public health crisis that demands the timely creation of new therapeutics and viral detection. Owing to their high specificity reliability, monoclonal antibodies (mAbs) have emerged as powerful tools treat detect numerous diseases. Hence, many researchers begun urgently develop Ab-based kits for detection severe acute respiratory syndrome 2 (SARS-CoV-2) Ab drugs use COVID-19 therapeutic agents. detailed structure SARS-CoV-2 spike protein known, since this key infection, its receptor-binding domain (RBD) has become a major target development. Because RNA virus with mutation rate, especially under selective pressure aggressively deployed prophylactic vaccines neutralizing Abs, cocktails expected be important strategy effective treatment. Moreover, infection may stimulate overactive immune response, resulting in cytokine storm drives progression. Abs combat storms also been intense development treatments COVID-19. In addition drugs, are currently being utilized tests, including antigen immunoglobulin tests. Such tests crucial surveillance can used prevent spread Herein, we highlight some points regarding mAb-based pandemic.

Language: Английский

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Antigenicity and receptor affinity of SARS-CoV-2 BA.2.86 spike

Nature, Journal Year: 2023, Volume and Issue: 624(7992), P. 639 - 644

Published: Oct. 23, 2023

Language: Английский

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Repeated Omicron exposures override ancestral SARS-CoV-2 immune imprinting

Nature, Journal Year: 2023, Volume and Issue: 625(7993), P. 148 - 156

Published: Nov. 22, 2023

Abstract The continuing emergence of SARS-CoV-2 variants highlights the need to update COVID-19 vaccine compositions. However, immune imprinting induced by vaccination based on ancestral (hereafter referred as WT) strain would compromise antibody response Omicron-based boosters 1–5 . Vaccination strategies counter are critically needed. Here we investigated degree and dynamics in mouse models human cohorts, especially focusing role repeated Omicron stimulation. In mice, efficacy single boosting is heavily limited when using that antigenically distinct from WT—such XBB variant—and this concerning situation could be mitigated a second booster. Similarly, humans, infections alleviate WT vaccination-induced generate broad neutralization responses both plasma nasal mucosa. Notably, deep mutational scanning-based epitope characterization 781 receptor-binding domain (RBD)-targeting monoclonal antibodies isolated infection revealed double exposure induce large proportion matured Omicron-specific have RBD epitopes WT-induced antibodies. Consequently, was largely mitigated, bias towards non-neutralizing observed exposures restored. On basis scanning profiles, identified evolution hotspots XBB.1.5 demonstrated these mutations further boost immune-evasion capability while maintaining high ACE2-binding affinity. Our findings suggest component should abandoned updating vaccines, individuals without prior receive two updated boosters.

Language: Английский

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A Comprehensive Review of the Protein Subunit Vaccines Against COVID-19

Frontiers in Microbiology, Journal Year: 2022, Volume and Issue: 13

Published: July 14, 2022

Two years after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), in December 2019, the first infections were identified Wuhan city of China. SARS-CoV-2 infection caused a global pandemic and accordingly, 5.41 million deaths worldwide. Hence, developing safe efficient vaccine for coronavirus disease 2019 (COVID-19) seems to be an urgent need. Attempts produce vaccines inexhaustibly are ongoing. At present time, according COVID-19 tracker landscape provided by World Health Organization (WHO), there 161 candidates different clinical phases all over world. In between, protein subunit types that contain viral like spike or its segment as antigen assumed elicit humoral cellular immunity good protective effects. Previously, this technology manufacturing was used recombinant influenza (RIV4). work, we review passing their phase 3 4 trials, population participated these manufactures, efficiency side effects, other features vaccines.

Language: Английский

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