Protective neutralizing epitopes in SARS‐CoV‐2 DOI

Hejun Liu,

Ian A. Wilson

Immunological Reviews, Journal Year: 2022, Volume and Issue: 310(1), P. 76 - 92

Published: May 22, 2022

Abstract The COVID‐19 pandemic has caused an unprecedented health crisis and economic burden worldwide. Its etiological agent SARS‐CoV‐2, a new virus in the coronavirus family, infected hundreds of millions people SARS‐CoV‐2 evolved over past 2 years to increase its transmissibility as well evade immunity established by previous infection vaccination. Nevertheless, strong immune responses can be elicited viral vaccination, which have proved protective against emergence variants, particularly with respect hospitalization or severe disease. Here, we review our current understanding how enters host cell system is able defend entry infection. Neutralizing antibodies are major component defense been extensively studied for variants. Structures these neutralizing provided valuable insights into epitopes that original ancestral variants emerged. molecular characterization epitope conservation resistance important design next‐generation vaccines antibody therapeutics.

Language: Английский

Broadly neutralizing antibodies to SARS-CoV-2 and other human coronaviruses DOI Open Access
Yanjia Chen, Xiaoyu Zhao, Hao Zhou

et al.

Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 23(3), P. 189 - 199

Published: Sept. 27, 2022

Language: Английский

Citations

283
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

243
Monoclonal antibody therapies against SARS-CoV-2 DOI Open Access
Daniele Focosi, Scott A. McConnell, Arturo Casadevall

et al.

The Lancet Infectious Diseases, Journal Year: 2022, Volume and Issue: 22(11), P. e311 - e326

Published: July 5, 2022

Language: Английский

Citations

215
Broadly neutralizing antibodies target the coronavirus fusion peptide DOI Creative Commons
Cherrelle Dacon, Courtney Tucker, Linghang Peng

et al.

Science, Journal Year: 2022, Volume and Issue: 377(6607), P. 728 - 735

Published: July 12, 2022

The potential for future coronavirus outbreaks highlights the need to broadly target this group of pathogens. We used an epitope-agnostic approach identify six monoclonal antibodies that bind spike proteins from all seven human-infecting coronaviruses. All conserved fusion peptide region adjacent S2' cleavage site. COV44-62 and COV44-79 neutralize alpha- betacoronaviruses, including severe acute respiratory syndrome 2 (SARS-CoV-2) Omicron subvariants BA.2 BA.4/5, albeit with lower potency than receptor binding domain-specific antibodies. In crystal structures antigen-binding fragments SARS-CoV-2 peptide, epitope adopts a helical structure includes arginine residue at limited disease caused by in Syrian hamster model. These findings highlight as candidate next-generation vaccine development.

Language: Английский

Citations

194
ACE2-binding exposes the SARS-CoV-2 fusion peptide to broadly neutralizing coronavirus antibodies DOI Creative Commons
Jun Siong Low, Josipa Jerak, M. Alejandra Tortorici

et al.

Science, Journal Year: 2022, Volume and Issue: 377(6607), P. 735 - 742

Published: July 12, 2022

The coronavirus spike glycoprotein attaches to host receptors and mediates viral fusion. Using a broad screening approach, we isolated seven monoclonal antibodies (mAbs) that bind all human-infecting proteins from severe acute respiratory syndrome 2 (SARS-CoV-2) immune donors. These mAbs recognize the fusion peptide acquire affinity breadth through somatic mutations. Despite targeting conserved motif, only some show neutralizing activity in vitro against alpha- betacoronaviruses, including animal coronaviruses WIV-1 PDF-2180. Two selected also neutralize Omicron BA.1 BA.2 authentic viruses reduce burden pathology vivo. Structural functional analyses showed peptide–specific bound with different modalities cryptic epitope hidden prefusion stabilized spike, which became exposed upon binding of angiotensin-converting enzyme (ACE2) or ACE2-mimicking mAbs.

Language: Английский

Citations

147
The impact of pre-existing cross-reactive immunity on SARS-CoV-2 infection and vaccine responses DOI Open Access
Sam M. Murray, M. Azim Ansari, John Frater

et al.

Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 23(5), P. 304 - 316

Published: Dec. 20, 2022

Language: Английский

Citations

124
Antibody-mediated neutralization of SARS-CoV-2 DOI Creative Commons

Henning Gruell,

Kanika Vanshylla, Timm Weber

et al.

Immunity, Journal Year: 2022, Volume and Issue: 55(6), P. 925 - 944

Published: May 13, 2022

Language: Английский

Citations

120
Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause deadly disease DOI Creative Commons
Pan-Pan Zhou, Ge Song,

Hejun Liu

et al.

Immunity, Journal Year: 2023, Volume and Issue: 56(3), P. 669 - 686.e7

Published: Feb. 16, 2023

Pan-betacoronavirus neutralizing antibodies may hold the key to developing broadly protective vaccines against novel pandemic coronaviruses and more effectively respond SARS-CoV-2 variants. The emergence of Omicron subvariants illustrates limitations solely targeting receptor-binding domain (RBD) spike (S) protein. Here, we isolated a large panel (bnAbs) from recovered-vaccinated donors, which targets conserved S2 region in betacoronavirus fusion machinery. Select bnAbs showed broad vivo protection all three deadly betacoronaviruses, SARS-CoV-1, SARS-CoV-2, MERS-CoV, have spilled over into humans past two decades. Structural studies these delineated molecular basis for their reactivity revealed common antibody features targetable by vaccination strategies. These provide new insights opportunities antibody-based interventions pan-betacoronavirus vaccines.

Language: Английский

Citations

120
Neutralization mechanism of a human antibody with pan-coronavirus reactivity including SARS-CoV-2 DOI Open Access
Xiaoyu Sun, Chunyan Yi, Yuanfei Zhu

et al.

Nature Microbiology, Journal Year: 2022, Volume and Issue: 7(7), P. 1063 - 1074

Published: June 30, 2022

Language: Английский

Citations

118
Close relatives of MERS-CoV in bats use ACE2 as their functional receptors DOI Creative Commons
Qing Xiong, Lei Cao,

Chengbao Ma

et al.

Nature, Journal Year: 2022, Volume and Issue: 612(7941), P. 748 - 757

Published: Dec. 7, 2022

Middle East respiratory syndrome coronavirus (MERS-CoV) and several bat coronaviruses use dipeptidyl peptidase-4 (DPP4) as an entry receptor1-4. However, the receptor for NeoCoV-the closest known MERS-CoV relative found in bats-remains unclear5. Here, using a pseudotype virus assay, we that NeoCoV its close relative, PDF-2180, can efficiently bind to specific angiotensin-converting enzyme 2 (ACE2) orthologues and, less favourably, human ACE2 receptors through their receptor-binding domains (RBDs) on spike (S) proteins. Cryo-electron microscopy analysis revealed RBD-ACE2 binding interface involving protein-glycan interactions, distinct from those of other ACE2-using coronaviruses. We identified residues 337-342 molecular determinant restricting entry, whereas S pseudotyped containing T510F RBD mutation entered cells expressing ACE2. Although polyclonal SARS-CoV-2 antibodies or RBD-specific nanobodies did not cross-neutralize ACE2-specific antibody two broadly neutralizing betacoronavirus inhibited these viruses. describe MERS-CoV-related viruses receptor, underscoring promiscuity potential zoonotic threat.

Language: Английский

Citations

105