文献检索文档翻译深度研究
Suppr Zotero 插件Zotero 插件
邀请有礼套餐&价格历史记录

新学期，新优惠

限时优惠:9月1日-9月22日

30天高级会员仅需29元

1天体验卡首发特惠仅需5.99元

了解详情
不再提醒
插件&应用
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
高级版
套餐订阅购买积分包
AI 工具
文献检索文档翻译深度研究
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2025

Prefusion-stabilized SARS-CoV-2 S2-only antigen provides protection against SARS-CoV-2 challenge.

Prefusion-stabilized SARS-CoV-2 S2-only antigen provides protection against SARS-CoV-2 challenge.

机构信息

Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, 78712, USA.

Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.

出版信息

Nat Commun. 2024 Feb 20;15(1):1553. doi: 10.1038/s41467-024-45404-x.

DOI:10.1038/s41467-024-45404-x
PMID:38378768
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10879192/
Abstract

Ever-evolving SARS-CoV-2 variants of concern (VOCs) have diminished the effectiveness of therapeutic antibodies and vaccines. Developing a coronavirus vaccine that offers a greater breadth of protection against current and future VOCs would eliminate the need to reformulate COVID-19 vaccines. Here, we rationally engineer the sequence-conserved S2 subunit of the SARS-CoV-2 spike protein and characterize the resulting S2-only antigens. Structural studies demonstrate that the introduction of interprotomer disulfide bonds can lock S2 in prefusion trimers, although the apex samples a continuum of conformations between open and closed states. Immunization with prefusion-stabilized S2 constructs elicits broadly neutralizing responses against several sarbecoviruses and protects female BALB/c mice from mouse-adapted SARS-CoV-2 lethal challenge and partially protects female BALB/c mice from mouse-adapted SARS-CoV lethal challenge. These engineering and immunogenicity results should inform the development of next-generation pan-coronavirus therapeutics and vaccines.

摘要

不断进化的严重急性呼吸综合征冠状病毒 2 型变异株（VOC）降低了治疗性抗体和疫苗的有效性。开发一种能够针对当前和未来的 VOC 提供更广泛保护的冠状病毒疫苗，将消除对 COVID-19 疫苗进行重新配方的需要。在这里，我们对 SARS-CoV-2 刺突蛋白的序列保守 S2 亚基进行了合理的工程改造，并对由此产生的 S2 单体抗原进行了表征。结构研究表明，引入同二硫键可以将 S2 锁定在预融合三聚体中，尽管尖峰样本在开放和闭合状态之间呈现连续的构象。用预融合稳定的 S2 构建体免疫可引发针对几种sarbecovirus 的广泛中和反应，并保护雌性 BALB/c 小鼠免受适应小鼠的 SARS-CoV-2 致死性挑战，并部分保护雌性 BALB/c 小鼠免受适应小鼠的 SARS-CoV 致死性挑战。这些工程和免疫原性结果应能为下一代泛冠状病毒治疗药物和疫苗的开发提供信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df6e/10879192/69e796d6d0b9/41467_2024_45404_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df6e/10879192/fa3d5b20592b/41467_2024_45404_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df6e/10879192/eee0a4643ffc/41467_2024_45404_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df6e/10879192/426d883babd1/41467_2024_45404_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df6e/10879192/f9b9d9b56238/41467_2024_45404_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df6e/10879192/7ad103e8fa77/41467_2024_45404_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df6e/10879192/1c4ddff2ce1b/41467_2024_45404_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df6e/10879192/69e796d6d0b9/41467_2024_45404_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df6e/10879192/fa3d5b20592b/41467_2024_45404_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df6e/10879192/eee0a4643ffc/41467_2024_45404_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df6e/10879192/426d883babd1/41467_2024_45404_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df6e/10879192/f9b9d9b56238/41467_2024_45404_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df6e/10879192/7ad103e8fa77/41467_2024_45404_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df6e/10879192/1c4ddff2ce1b/41467_2024_45404_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df6e/10879192/69e796d6d0b9/41467_2024_45404_Fig7_HTML.jpg

相似文献

[1]
Prefusion-stabilized SARS-CoV-2 S2-only antigen provides protection against SARS-CoV-2 challenge.

Nat Commun. 2024-2-20

[2]
A broadly generalizable stabilization strategy for sarbecovirus fusion machinery vaccines.

Nat Commun. 2024-6-28

[3]
SARS-CoV-2 Spike Protein Stabilized in the Closed State Induces Potent Neutralizing Responses.

J Virol. 2021-7-12

[4]
Simulation-driven design of stabilized SARS-CoV-2 spike S2 immunogens.

Nat Commun. 2024-8-27

[5]
A Single Dose of an MVA Vaccine Expressing a Prefusion-Stabilized SARS-CoV-2 Spike Protein Neutralizes Variants of Concern and Protects Mice From a Lethal SARS-CoV-2 Infection.

Front Immunol. 2021

[6]
Trivalent NDV-HXP-S Vaccine Protects against Phylogenetically Distant SARS-CoV-2 Variants of Concern in Mice.

Microbiol Spectr. 2022-6-29

[7]
Surface-modified measles vaccines encoding oligomeric, prefusion-stabilized SARS-CoV-2 spike glycoproteins boost neutralizing antibody responses to Omicron and historical variants, independent of measles seropositivity.

mBio. 2024-2-14

[8]
A circular mRNA vaccine prototype producing VFLIP-X spike confers a broad neutralization of SARS-CoV-2 variants by mouse sera.

Antiviral Res. 2022-8

[9]
Multi-antigen intranasal vaccine protects against challenge with sarbecoviruses and prevents transmission in hamsters.

Nat Commun. 2024-7-23

[10]
A next-generation intranasal trivalent MMS vaccine induces durable and broad protection against SARS-CoV-2 variants of concern.

Proc Natl Acad Sci U S A. 2023-10-10

引用本文的文献

[1]
A nanobody specific to prefusion glycoprotein B neutralizes HSV-1 and HSV-2.

Nature. 2025-9-3

[2]
Bivalent mRNA booster encoding virus-like particles elicits potent polyclass RBD antibodies in pre-vaccinated mice.

bioRxiv. 2025-8-19

[3]
Merbecovirus S2 subunit vaccines elicit cross reactive antibodies and provide partial protection against MERS coronavirus.

Npj Viruses. 2025-7-29

[4]
Structural stabilization of the intrinsically disordered SARS-CoV-2 N by binding to RNA sequences engineered from the viral genome fragment.

Nat Commun. 2025-7-15

[5]
Targeting heptad repeats and fusion peptide: nanoparticle vaccine elicits mucosal immune response against SARS-CoV-2 variants.

J Nanobiotechnology. 2025-7-3

[6]
Beyond the Pandemic Era: Recent Advances and Efficacy of SARS-CoV-2 Vaccines Against Emerging Variants of Concern.

Vaccines (Basel). 2025-4-17

[7]
Making Universal Vaccines and Antibodies Through Glycoengineering.

Methods Mol Biol. 2025

[8]
Public antibodies: convergent signatures in human humoral immunity against pathogens.

mBio. 2025-5-14

[9]
Mechanistic insights into the structure-based design of a CspZ-targeting Lyme disease vaccine.

Nat Commun. 2025-4-7

[10]
RBD-depleted SARS-CoV-2 spike generates protective immunity in cynomolgus macaques.

NPJ Vaccines. 2025-3-30

本文引用的文献

[1]
SARS-COV-2 Omicron variants conformationally escape a rare quaternary antibody binding mode.

Commun Biol. 2023-12-11

[2]
Bivalent omicron (BA.1) booster vaccination against SARS-CoV-2.

Lancet Infect Dis. 2023-8

[3]
Fc-mediated pan-sarbecovirus protection after alphavirus vector vaccination.

Cell Rep. 2023-4-25

[4]
Identification of a conserved S2 epitope present on spike proteins from all highly pathogenic coronaviruses.

Elife. 2023-3-21

[5]
The rapid rise of SARS-CoV-2 Omicron subvariants with immune evasion properties: XBB.1.5 and BQ.1.1 subvariants.

MedComm (2020). 2023-3-15

[6]
Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause deadly disease.

Immunity. 2023-3-14

[7]
XBB.1.5 neutralizing antibodies upon bivalent COVID-19 vaccination are similar to XBB but lower than BQ.1.1.

Am J Hematol. 2023-5

[8]
Human neutralizing antibodies to cold linear epitopes and subdomain 1 of the SARS-CoV-2 spike glycoprotein.

Sci Immunol. 2023-3-17

[9]
Mosaic RBD nanoparticles induce intergenus cross-reactive antibodies and protect against SARS-CoV-2 challenge.

Proc Natl Acad Sci U S A. 2023-1-24

[10]
SARS-CoV-2 variant biology: immune escape, transmission and fitness.

Nat Rev Microbiol. 2023-3

文献AI研究员

20分钟写一篇综述，助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

推荐工具

医学文档翻译智能文献检索