Cryo-EM structures of SARS-CoV-2 Omicron BA.2 spike DOI Creative Commons
Victoria Stalls, Jared Lindenberger, S. Gobeil

et al.

Cell Reports, Journal Year: 2022, Volume and Issue: 39(13), P. 111009 - 111009

Published: June 1, 2022

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2 sub-lineage has gained in proportion relative to BA.1. Because spike (S) protein variations may underlie differences their pathobiology, here we determine cryoelectron microscopy (cryo-EM) structures of the S ectodomain and compare these with previously determined BA.1 structures. receptor-binding domain (RBD) mutations induce remodeling RBD structure, resulting tighter packing improved thermostability. Interprotomer interactions are enhanced closed (or 3-RBD-down) S, while fusion peptide is less accessible antibodies than Binding pseudovirus neutralization assays reveal extensive immune evasion defining epitopes two outer face-binding antibodies, DH1044 DH1193, that neutralize both BA.2. Taken together, our results indicate stabilization state through interprotomer RBD-RBD a hallmark variant show key functional regions proteins.

Language: Английский

Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2 DOI Open Access
Lihong Liu, Sho Iketani, Yicheng Guo

et al.

Nature, Journal Year: 2021, Volume and Issue: 602(7898), P. 676 - 681

Published: Dec. 23, 2021

Language: Английский

Citations

1263
Antibody evasion properties of SARS-CoV-2 Omicron sublineages DOI Creative Commons
Sho Iketani, Lihong Liu, Yicheng Guo

et al.

Nature, Journal Year: 2022, Volume and Issue: 604(7906), P. 553 - 556

Published: March 3, 2022

The identification of the Omicron (B.1.1.529.1 or BA.1) variant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Botswana November 2021

Language: Английский

Citations

790
Antibody evasion by SARS-CoV-2 Omicron subvariants BA.2.12.1, BA.4 and BA.5 DOI Creative Commons
Qian Wang, Yicheng Guo, Sho Iketani

et al.

Nature, Journal Year: 2022, Volume and Issue: 608(7923), P. 603 - 608

Published: July 5, 2022

Abstract SARS-CoV-2 Omicron subvariants BA.2.12.1 and BA.4/5 have surged notably to become dominant in the United States South Africa, respectively 1,2 . These new carrying further mutations their spike proteins raise concerns that they may evade neutralizing antibodies, thereby compromising efficacy of COVID-19 vaccines therapeutic monoclonals. We now report findings from a systematic antigenic analysis these surging subvariants. is only modestly (1.8-fold) more resistant sera vaccinated boosted individuals than BA.2. However, substantially (4.2-fold) thus likely lead vaccine breakthrough infections. Mutation at residue L452 found both facilitates escape some antibodies directed so-called class 2 3 regions receptor-binding domain The F486V mutation certain 1 but compromises affinity for viral receptor. R493Q reversion mutation, however, restores receptor consequently fitness BA.4/5. Among authorized clinical use, bebtelovimab retains full potency against lineage continues evolve, successively yielding are not transmissible also evasive antibodies.

Language: Английский

Citations

714
Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants DOI Creative Commons
Meng Yuan, Deli Huang, Chang‐Chun D. Lee

et al.

Science, Journal Year: 2021, Volume and Issue: 373(6556), P. 818 - 823

Published: May 21, 2021

Neutralizing antibodies (nAbs) elicited against the receptor binding site (RBS) of spike protein wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are generally less effective recent variants concern. RBS residues Glu

Language: Английский

Citations

367
Membrane fusion and immune evasion by the spike protein of SARS-CoV-2 Delta variant DOI Creative Commons
Jun Zhang, Tianshu Xiao, Yongfei Cai

et al.

Science, Journal Year: 2021, Volume and Issue: 374(6573), P. 1353 - 1360

Published: Oct. 26, 2021

Delta’s spike Understanding the molecular mechanisms of increased transmissibility and immune evasion severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is critical to guiding current future intervention strategies. Zhang et al . determined cryo–electron microscopy structures full-length protein trimers Delta, Kappa, Gamma SARS-CoV-2 studied their function antigenic properties. The Delta fused membranes more efficiently at low levels cellular receptor ACE2, its pseudotyped viruses infected target cells substantially rapidly than all other tested, possibly least partly accounting for heightened transmissibility. Mutations each variant rearranged surface N-terminal domain but only caused local changes in receptor-binding domain, consistent with greater resistance neutralizing antibodies. These findings elucidate events that have led these adapt human communities evade host immunity. —VV

Language: Английский

Citations

291
Anti-SARS-CoV-2 receptor-binding domain antibody evolution after mRNA vaccination DOI Creative Commons
Alice Cho,

Frauke Muecksch,

Dennis Schaefer-Babajew

et al.

Nature, Journal Year: 2021, Volume and Issue: 600(7889), P. 517 - 522

Published: Oct. 7, 2021

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection produces B cell responses that continue to evolve for at least a year. During time, memory cells express increasingly broad and potent antibodies are resistant mutations found in variants of concern 1 . As result, vaccination disease 2019 (COVID-19) convalescent individuals with currently available mRNA vaccines high levels plasma neutralizing activity against all tested 1,2 Here we examine evolution five months after either Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccine cohort SARS-CoV-2-naive individuals. Between prime boost, produce increased activity, but there is no further increase potency breadth thereafter. Instead, emerge naive similar those dominate the initial response. While individual selected over time by natural have greater than elicited vaccination, overall following vaccination. These results suggest boosting vaccinated will may not equivalent obtained vaccinating

Language: Английский

Citations

279
Correlates of protection against SARS‐CoV‐2 infection and COVID‐19 disease DOI
David Goldblatt, Galit Alter, Shane Crotty

et al.

Immunological Reviews, Journal Year: 2022, Volume and Issue: 310(1), P. 6 - 26

Published: June 5, 2022

Antibodies against epitopes in S1 give the most accurate CoP infection by SARS-CoV-2 coronavirus. Measurement of those antibodies neutralization or binding assays both have predictive value, with antibody titers giving highest statistical correlation. However, protective functions are multiple. multiple other than influence efficacy. The role cellular responses can be discerned respect to CD4

Language: Английский

Citations

241
Monoclonal antibodies for COVID-19 therapy and SARS-CoV-2 detection DOI Creative Commons
Yu‐Chyi Hwang, Ruei‐Min Lu,

Shih-Chieh Su

et al.

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

Citations

205
Large-Scale Study of Antibody Titer Decay following BNT162b2 mRNA Vaccine or SARS-CoV-2 Infection DOI Creative Commons
Ariel Israel,

Yotam Shenhar,

Ilan Green

et al.

Vaccines, Journal Year: 2021, Volume and Issue: 10(1), P. 64 - 64

Published: Dec. 31, 2021

Immune protection following either vaccination or infection with SARS-CoV-2 is thought to decrease over time. We designed a retrospective study, conducted at Leumit Health Services in Israel, determine the kinetics of IgG antibodies administration two doses BNT162b2 vaccine, unvaccinated individuals. Antibody titers were measured between 31 January 2021, and July 2021 mutually exclusive groups: (i) vaccinated individuals who received vaccine had no history previous COVID-19 (ii) convalescents not vaccine. A total 2653 fully by during study period 4361 convalescent patients included. Higher antibody observed (median 1581 AU/mL IQR [533.8-5644.6]) after second than 355.3 [141.2-998.7]; p < 0.001). In subjects, decreased up 38% each subsequent month while they less 5% per month. Six months 16.1% subjects levels below seropositivity threshold <50 AU/mL, only 10.8% 9 from infection. This demonstrates Pfizer-BioNTech mRNA have different compared been infected virus, higher initial but much faster exponential first group.

Language: Английский

Citations

191
The SARS-CoV-2 Lambda variant exhibits enhanced infectivity and immune resistance DOI

Izumi Kimura,

Yusuke Kosugi,

Jiaqi Wu

et al.

Cell Reports, Journal Year: 2021, Volume and Issue: 38(2), P. 110218 - 110218

Published: Dec. 18, 2021

Language: Английский

Citations

181