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默贝科病毒S2亚基疫苗可引发交叉反应性抗体,并对中东呼吸综合征冠状病毒提供部分保护。

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

作者信息

Halfmann Peter J, Lee Jeong Soo, Duffy Augustine, Huang Bingcheng, Yang Jie E, Wright Elizabeth R, Kawaoka Yoshihiro, Kane Ravi S

机构信息

Department of Pathobiological Sciences, Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA.

School of Chemical & Biomolecular Engineering, Georgia Institute of Technology, Atlanta, GA, USA.

出版信息

Npj Viruses. 2025 Jul 29;3(1):60. doi: 10.1038/s44298-025-00142-9.


DOI:10.1038/s44298-025-00142-9
PMID:40730716
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12307638/
Abstract

Since the outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV), a virus that has caused a high case fatality rate of 36%, other merbecoviruses have been reported to also be capable of infecting human cells. Given the threat of Merbecovirus spillover to humans, we developed virus-like particle vaccines presenting the S2 subunit proteins of MERS-CoV, NeoCoV, HKU4, or HKU25. Mice were vaccinated with the homotypic vaccines, and IgG endpoint titers were measured against S2 proteins of the same panel of viruses, confirming high cross-reactivity across all four viruses. Based on characterization by antigenic cartography, MERS-CoV and HKU4 S2 proteins were selected as optimal components for a cocktail vaccine. MERS-CoV and NeoCoV homotypic vaccines, along with the mixture vaccine, provided partial protection in transgenic mice against a MERS-CoV challenge. These findings could serve as an important step toward designing pan-Merbecovirus vaccines in preparation for future outbreaks.

摘要

自中东呼吸综合征冠状病毒(MERS-CoV)爆发以来,这种病毒的病死率高达36%,据报道其他默贝病毒也能够感染人类细胞。鉴于默贝病毒向人类溢出的威胁,我们开发了呈现MERS-CoV、NeoCoV、HKU4或HKU25的S2亚基蛋白的病毒样颗粒疫苗。用同型疫苗对小鼠进行免疫接种,并针对同一组病毒的S2蛋白测量IgG终点滴度,证实所有四种病毒之间具有高交叉反应性。基于抗原图谱分析,MERS-CoV和HKU4的S2蛋白被选为混合疫苗的最佳成分。MERS-CoV和NeoCoV同型疫苗以及混合疫苗为转基因小鼠抵御MERS-CoV攻击提供了部分保护。这些发现可能是朝着设计泛默贝病毒疫苗迈出的重要一步,为未来的疫情爆发做好准备。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/208e/12307638/983bab04010a/44298_2025_142_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/208e/12307638/26fa30a40cfb/44298_2025_142_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/208e/12307638/817f1f35c2e5/44298_2025_142_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/208e/12307638/f7347b88ae97/44298_2025_142_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/208e/12307638/23f856606eb1/44298_2025_142_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/208e/12307638/5d93ec14d258/44298_2025_142_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/208e/12307638/983bab04010a/44298_2025_142_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/208e/12307638/26fa30a40cfb/44298_2025_142_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/208e/12307638/817f1f35c2e5/44298_2025_142_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/208e/12307638/f7347b88ae97/44298_2025_142_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/208e/12307638/23f856606eb1/44298_2025_142_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/208e/12307638/5d93ec14d258/44298_2025_142_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/208e/12307638/983bab04010a/44298_2025_142_Fig6_HTML.jpg

相似文献

[1]
Merbecovirus S2 subunit vaccines elicit cross reactive antibodies and provide partial protection against MERS coronavirus.

Npj Viruses. 2025-7-29

[2]
Cross-neutralization ability of anti-MERS-CoV monoclonal antibodies against a variety of merbecoviruses.

Front Microbiol. 2025-7-16

[3]
and characterization of a bat merbecovirus with ACE2- and DPP4-independent cell entry.

J Virol. 2025-7-22

[4]
A single-dose intranasal immunization with a novel bat influenza A virus-vectored MERS vaccine provides effective protection against lethal MERS-CoV challenge.

mBio. 2025-6-30

[5]
Designing Sandwich ELISA with Broadly Reactive Anti-Nucleocapsid Monoclonal Antibodies to Detect Bat-Borne Merbecoviruses.

Viruses. 2025-6-24

[6]
Safety, immunogenicity, and optimal dosing of a modified vaccinia Ankara-based vaccine against MERS-CoV in healthy adults: a phase 1b, double-blind, randomised placebo-controlled clinical trial.

Lancet Infect Dis. 2025-2

[7]
Antibody tests for identification of current and past infection with SARS-CoV-2.

Cochrane Database Syst Rev. 2022-11-17

[8]
Safety and immunogenicity of a modified mRNA-lipid nanoparticle vaccine candidate against COVID-19: Results from a phase 1, dose-escalation study.

Hum Vaccin Immunother. 2024-12-31

[9]
Establishment of a Sandwich ELISA for Detection of Pan-Merbecoviruses.

Pathogens. 2025-6-19

[10]
COVID-19 Vaccines

2006

本文引用的文献

[1]
ACE2 from Pipistrellus abramus bats is a receptor for HKU5 coronaviruses.

Nat Commun. 2025-5-28

[2]
Bat-infecting merbecovirus HKU5-CoV lineage 2 can use human ACE2 as a cell entry receptor.

Cell. 2025-3-20

[3]
Molecular basis of convergent evolution of ACE2 receptor utilization among HKU5 coronaviruses.

Cell. 2025-3-20

[4]
Multivalent S2 subunit vaccines provide broad protection against Clade 1 sarbecoviruses in female mice.

Nat Commun. 2025-1-7

[5]
A broadly generalizable stabilization strategy for sarbecovirus fusion machinery vaccines.

Nat Commun. 2024-6-28

[6]
Proactive vaccination using multiviral Quartet Nanocages to elicit broad anti-coronavirus responses.

Nat Nanotechnol. 2024-8

[7]
Prefusion-stabilized SARS-CoV-2 S2-only antigen provides protection against SARS-CoV-2 challenge.

Nat Commun. 2024-2-20

[8]
Broad protection against clade 1 sarbecoviruses after a single immunization with cocktail spike-protein-nanoparticle vaccine.

Nat Commun. 2024-2-12

[9]
Isolation and characterization of a pangolin-borne HKU4-related coronavirus that potentially infects human-DPP4-transgenic mice.

Nat Commun. 2024-2-5

[10]
Engineered immunogens to elicit antibodies against conserved coronavirus epitopes.

Nat Commun. 2023-11-30

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