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

A large-scale systematic survey reveals recurring molecular features of public antibody responses to SARS-CoV-2 DOI Creative Commons
Yiquan Wang, Meng Yuan, Huibin Lv

et al.

Immunity, Journal Year: 2022, Volume and Issue: 55(6), P. 1105 - 1117.e4

Published: March 25, 2022

Global research to combat the COVID-19 pandemic has led isolation and characterization of thousands human antibodies SARS-CoV-2 spike protein, providing an unprecedented opportunity study antibody response a single antigen. Using information derived from 88 publications 13 patents, we assembled dataset ∼8,000 protein >200 donors. By analyzing immunoglobulin V D gene usages, complementarity-determining region H3 sequences, somatic hypermutations, demonstrated that common (public) responses different domains were quite different. We further used these sequences train deep-learning model accurately distinguish between those influenza hemagglutinin protein. Overall, this provides informative resource for enhances our molecular understanding public responses.

Language: Английский

Citations

91
Antiviral Drug Discovery for the Treatment of COVID-19 Infections DOI Creative Commons
Teresa I. Ng, Ivan Correia, Jane Seagal

et al.

Viruses, Journal Year: 2022, Volume and Issue: 14(5), P. 961 - 961

Published: May 4, 2022

The coronavirus disease 2019 (COVID-19) pandemic is caused by the severe acute respiratory syndrome 2 (SARS-CoV-2), a recently emerged human coronavirus. COVID-19 vaccines have proven to be successful in protecting vaccinated from infection, reducing severity of disease, and deterring transmission infection. However, vaccination faces many challenges, such as decline vaccine-induced immunity over time, decrease potency against some SARS-CoV-2 variants including Omicron variant, resulting breakthrough infections. challenges that facing highlight importance discovery antivirals serve another means tackle pandemic. To date, neutralizing antibodies block viral entry targeting spike protein make up largest class has received US FDA emergency use authorization (EUA) for treatment. In addition protein, other key targets direct-acting include enzymes are essential replication, RNA-dependent RNA polymerase proteases, judged approval remdesivir, EUA Paxlovid (nirmatrelvir + ritonavir) treating This review presents an overview current status future direction antiviral drug infections, covering important non-structural (nsp) 3 papain-like protease, nsp5 main nsp12/nsp7/nsp8 complex.

Language: Английский

Citations

80
SARS-CoV-2 spike conformation determines plasma neutralizing activity elicited by a wide panel of human vaccines DOI Creative Commons
John E. Bowen, Young‐Jun Park, Cameron Stewart

et al.

Science Immunology, Journal Year: 2022, Volume and Issue: 7(78)

Published: Nov. 10, 2022

Numerous safe and effective coronavirus disease 2019 vaccines have been developed worldwide that use various delivery technologies engineering strategies. We show here containing prefusion-stabilizing S mutations elicit antibody responses in humans with enhanced recognition of the

Language: Английский

Citations

72
Human neutralizing antibodies to cold linear epitopes and subdomain 1 of the SARS-CoV-2 spike glycoprotein DOI Creative Commons
Filippo Bianchini, Virginia Crivelli, Morgan E. Abernathy

et al.

Science Immunology, Journal Year: 2023, Volume and Issue: 8(81)

Published: Jan. 26, 2023

Emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants diminishes the efficacy vaccines and antiviral monoclonal antibodies. Continued development immunotherapies vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions virus spike glycoprotein are both functionally relevant averse change, we identified human neutralizing antibodies highly conserved epitopes. Antibody fp.006 binds fusion peptide cross-reacts against coronaviruses four genera, including nine coronaviruses, through recognition motif includes S2' site proteolytic cleavage. hr2.016 targets stem helix neutralizes SARS-CoV-2 variants. sd1.040 subdomain 1, synergizes with rbd.042 for neutralization, and, similar hr2.016, protects mice expressing angiotensin-converting enzyme infection when present as bispecific antibody. Thus, discovery reveals donor-derived cross-reactive Orthocoronavirinae,

Language: Английский

Citations

67
Identification of a conserved S2 epitope present on spike proteins from all highly pathogenic coronaviruses DOI Creative Commons

Rui P. Silva,

Yimin Huang, Annalee W. Nguyen

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: March 21, 2023

To address the ongoing SARS-CoV-2 pandemic and prepare for future coronavirus outbreaks, understanding protective potential of epitopes conserved across variants lineages is essential. We describe a highly conserved, conformational S2 domain epitope present only in prefusion core β-coronaviruses: apex residues 980–1006 flexible hinge. Antibody RAY53 binds native hinge MERS-CoV spikes on surface mammalian cells mediates antibody-dependent cellular phagocytosis cytotoxicity against spike vitro. Hinge mutations that ablate antibody binding compromise pseudovirus infectivity, but changes elsewhere affect opening dynamics, including those found Omicron BA.1, occlude may evade pre-existing serum antibodies targeting core. This work defines third class while providing insights into potency limitations targeting.

Language: Английский

Citations

66
Persistent immune imprinting occurs after vaccination with the COVID-19 XBB.1.5 mRNA booster in humans DOI Creative Commons
M. Alejandra Tortorici, Amin Addetia,

Albert J. Seo

et al.

Immunity, Journal Year: 2024, Volume and Issue: 57(4), P. 904 - 911.e4

Published: March 14, 2024

Immune imprinting describes how the first exposure to a virus shapes immunological outcomes of subsequent exposures antigenically related strains. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron breakthrough infections and bivalent COVID-19 vaccination primarily recall cross-reactive memory B cells induced by prior Wuhan-Hu-1 spike mRNA rather than priming Omicron-specific naive cells. These findings indicate that immune occurs after repeated exposures, but whether it can be overcome remains unclear. To understand persistence imprinting, we investigated plasma antibody responses administration updated XBB.1.5 vaccine booster. We showed booster elicited neutralizing against current variants were dominated pre-existing previously spike. Therefore, persists multiple spikes through infection, including post vaccination, which will need considered guide future vaccination.

Language: Английский

Citations

59
Targetable elements in SARS-CoV-2 S2 subunit for the design of pan-coronavirus fusion inhibitors and vaccines DOI Creative Commons

Liyan Guo,

Sheng Lin, Zimin Chen

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: May 10, 2023

Abstract The ongoing global pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome 2 (SARS‐CoV‐2), has devastating impacts on the public health and economy. Rapid viral antigenic evolution led to continual generation new variants. Of special note is recently expanding Omicron subvariants that are capable immune evasion from most existing neutralizing antibodies (nAbs). This posed challenges for prevention treatment COVID-19. Therefore, exploring broad-spectrum antiviral agents combat emerging variants imperative. In sharp contrast massive accumulation mutations within SARS-CoV-2 receptor-binding domain (RBD), S2 fusion subunit remained highly conserved among Hence, S2-based therapeutics may provide effective cross-protection against Here, we summarize developed inhibitors (e.g., nAbs, peptides, proteins, small-molecule compounds) candidate vaccines targeting elements in subunit. main focus includes all targetable elements, namely, peptide, stem helix, heptad repeats 1 (HR1-HR2) bundle. Moreover, a detailed summary characteristics action-mechanisms each class cross-reactive inhibitors, which should guide promote future design coronaviruses.

Language: Английский

Citations

48
Imprinting of serum neutralizing antibodies by Wuhan-1 mRNA vaccines DOI
Chieh-Yu Liang, Saravanan Raju, Zhuoming Liu

et al.

Nature, Journal Year: 2024, Volume and Issue: 630(8018), P. 950 - 960

Published: May 15, 2024

Language: Английский

Citations

34
Structure and inhibition of SARS-CoV-2 spike refolding in membranes DOI
Michael W. Grunst, Zhuan Qin, Esteban Dodero‐Rojas

et al.

Science, Journal Year: 2024, Volume and Issue: 385(6710), P. 757 - 765

Published: Aug. 15, 2024

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein binds the receptor angiotensin converting enzyme (ACE2) and drives virus-host membrane fusion through refolding of its S2 domain. Whereas S1 domain contains high sequence variability, is conserved a promising pan-betacoronavirus vaccine target. We applied cryo-electron tomography to capture intermediates understand inhibition by antibodies stem-helix. Subtomogram averaging revealed ACE2 dimers cross-linking spikes before transitioning into intermediates, which were captured at various stages refolding. Pan-betacoronavirus neutralizing targeting stem-helix bound inhibited prehairpin intermediates. Combined with molecular dynamics simulations, these structures elucidate process SARS-CoV-2 entry reveal how S2-targeting neutralize infectivity arresting

Language: Английский

Citations

19
Challenges and developments in universal vaccine design against SARS-CoV-2 variants DOI Creative Commons
Fangxin Zhao, Xiaodong Zai, Zhiling Zhang

et al.

npj Vaccines, Journal Year: 2022, Volume and Issue: 7(1)

Published: Dec. 19, 2022

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had become a global concern because its unexpectedly high pathogenicity and transmissibility. SARS-CoV-2 variants that reduce the immune protection elicited from previous vaccination or natural infection raise challenges in controlling spread pandemic. development universal vaccines against these seems to be practical solution alleviate physical economic effects caused by this disease, but it is hard achieve. In review, we describe mutation rate RNA viruses dynamic molecular structures several major neutralizing epitopes, trying answer question why are difficult design. Understanding biological basis evasion crucial for combating obstacles. We then summarize advancements worthy further study, including heterologous prime-boost regimens, construction chimeric immunogens, design protein nanoparticle antigens, utilization conserved epitopes. fact some immunogens can induce cross-reactive responses coronaviruses provides hints vaccine development. hope review provide inspiration current studies.

Language: Английский

Citations

60