• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
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
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
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 @ 2026

文献检索

告别复杂PubMed语法,用中文像聊天一样搜索,搜遍4000万医学文献。AI智能推荐,让科研检索更轻松。

立即免费搜索

文件翻译

保留排版,准确专业,支持PDF/Word/PPT等文件格式,支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述,25分钟生成高质量综述,智能提取关键信息,辅助科研写作。

立即免费体验

一种基于嵌合型热稳定M2e和H3茎部的甲型流感病毒通用疫苗。

A chimeric thermostable M2e and H3 stalk-based universal influenza A virus vaccine.

作者信息

Subbiah Jeeva, Oh Judy, Kim Ki-Hye, Shin Chong-Hyun, Park Bo Ryoung, Bhatnagar Noopur, Seong Baik-Lin, Wang Bao-Zhong, Kang Sang-Moo

机构信息

Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, 30303, USA.

Department of Microbiology, College of Medicine, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.

出版信息

NPJ Vaccines. 2022 Jun 29;7(1):68. doi: 10.1038/s41541-022-00498-6.

DOI:10.1038/s41541-022-00498-6
PMID:35768475
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9243060/
Abstract

We developed a new chimeric M2e and H3 hemagglutinin (HA) stalk protein vaccine (M2e-H3 stalk) by genetic engineering of modified H3 stalk domain conjugated with conserved M2e epitopes to overcome the drawbacks of low efficacy by monomeric domain-based universal vaccines. M2e-H3 stalk protein expressed and purified from Escherichia coli was thermostable, displaying native-like antigenic epitopes recognized by antisera of different HA subtype proteins and influenza A virus infections. Adjuvanted M2e-H3 stalk vaccination induced M2e and stalk-specific IgG antibodies recognizing viral antigens on virus particles and on the infected cell surface, CD4 and CD8 T-cell responses, and antibody-dependent cytotoxic cell surrogate activity in mice. M2e-H3 stalk was found to confer protection against heterologous and heterosubtypic cross-group subtype viruses (H1N1, H5N1, H9N2, H3N2, H7N9) at similar levels in adult and aged mice. These results provide evidence that M2e-H3 stalk chimeric proteins can be developed as a universal influenza A virus vaccine candidate for young and aged populations.

摘要

我们通过对修饰的H3茎域进行基因工程改造,并将其与保守的M2e表位偶联,开发了一种新型嵌合M2e和H3血凝素(HA)茎蛋白疫苗(M2e-H3茎),以克服基于单体结构域的通用疫苗效力低下的缺点。从大肠杆菌中表达并纯化的M2e-H3茎蛋白具有热稳定性,展现出可被不同HA亚型蛋白抗血清和甲型流感病毒感染识别的类似天然的抗原表位。佐剂化的M2e-H3茎疫苗接种可诱导产生识别病毒颗粒和感染细胞表面病毒抗原的M2e和茎特异性IgG抗体、CD4和CD8 T细胞应答,以及小鼠体内抗体依赖性细胞毒性细胞替代活性。结果发现,M2e-H3茎在成年和老年小鼠中对异源和异亚型跨组亚型病毒(H1N1、H5N1、H9N2、H3N2、H7N9)具有相似水平的保护作用。这些结果证明,M2e-H3茎嵌合蛋白可开发成为针对年轻和老年人群的通用甲型流感病毒候选疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e36/9243060/8618c3783cd9/41541_2022_498_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e36/9243060/9b34a8b976aa/41541_2022_498_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e36/9243060/8f0383406e2e/41541_2022_498_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e36/9243060/225b51634994/41541_2022_498_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e36/9243060/d0de52512d2f/41541_2022_498_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e36/9243060/99df540af3e5/41541_2022_498_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e36/9243060/7ce8f35cba2e/41541_2022_498_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e36/9243060/623fa5e806d6/41541_2022_498_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e36/9243060/a69c61875240/41541_2022_498_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e36/9243060/8618c3783cd9/41541_2022_498_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e36/9243060/9b34a8b976aa/41541_2022_498_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e36/9243060/8f0383406e2e/41541_2022_498_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e36/9243060/225b51634994/41541_2022_498_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e36/9243060/d0de52512d2f/41541_2022_498_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e36/9243060/99df540af3e5/41541_2022_498_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e36/9243060/7ce8f35cba2e/41541_2022_498_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e36/9243060/623fa5e806d6/41541_2022_498_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e36/9243060/a69c61875240/41541_2022_498_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5e36/9243060/8618c3783cd9/41541_2022_498_Fig9_HTML.jpg

相似文献

1
A chimeric thermostable M2e and H3 stalk-based universal influenza A virus vaccine.一种基于嵌合型热稳定M2e和H3茎部的甲型流感病毒通用疫苗。
NPJ Vaccines. 2022 Jun 29;7(1):68. doi: 10.1038/s41541-022-00498-6.
2
Cross-protection against influenza viruses by chimeric M2e-H3 stalk protein or multi-subtype neuraminidase plus M2e virus-like particle vaccine in ferrets.嵌合 M2e-H3 茎蛋白或多亚型神经氨酸酶加 M2e 病毒样颗粒疫苗对雪貂流感病毒的交叉保护作用。
Virology. 2024 Jul;595:110097. doi: 10.1016/j.virol.2024.110097. Epub 2024 Apr 25.
3
Thermostable H1 hemagglutinin stem with M2e epitopes provides broad cross-protection against group1 and 2 influenza A viruses.带有M2e表位的热稳定H1血凝素茎部可提供针对1型和2型甲型流感病毒的广泛交叉保护。
Mol Ther Methods Clin Dev. 2022 May 29;26:38-51. doi: 10.1016/j.omtm.2022.05.007. eCollection 2022 Sep 8.
4
Enhanced cross protection by hetero prime-boost vaccination with recombinant influenza viruses containing chimeric hemagglutinin-M2e epitopes.含嵌合血凝素-M2e 表位的重组流感病毒异源初免-加强免疫可增强交叉保护作用。
Virology. 2022 Jan;566:143-152. doi: 10.1016/j.virol.2021.12.003. Epub 2021 Dec 10.
5
Cross protection by inactivated recombinant influenza viruses containing chimeric hemagglutinin conjugates with a conserved neuraminidase or M2 ectodomain epitope.含保守神经氨酸酶或 M2 胞外结构域表位嵌合血凝素缀合物的灭活重组流感病毒的交叉保护作用。
Virology. 2020 Nov;550:51-60. doi: 10.1016/j.virol.2020.08.003. Epub 2020 Aug 22.
6
An Inactivated Influenza Virus Vaccine Approach to Targeting the Conserved Hemagglutinin Stalk and M2e Domains.一种针对保守的血凝素茎部和M2e结构域的灭活流感病毒疫苗方法。
Vaccines (Basel). 2019 Sep 18;7(3):117. doi: 10.3390/vaccines7030117.
7
Intranasal adenovirus-vectored vaccine for induction of long-lasting humoral immunity-mediated broad protection against influenza in mice.用于诱导持久体液免疫介导的对小鼠流感广泛保护的鼻内腺病毒载体疫苗。
J Virol. 2014 Sep 1;88(17):9693-703. doi: 10.1128/JVI.00823-14. Epub 2014 Jun 11.
8
Characterization of Immune Response towards Generation of Universal Anti-HA-Stalk Antibodies after Immunization of Broiler Hens with Triple H5N1/NA-HA-M1 VLPs.免疫接种三重 H5N1/NA-HA-M1 VLP 后对产生通用抗 HA-茎部抗体的免疫反应进行表征。
Viruses. 2022 Mar 30;14(4):730. doi: 10.3390/v14040730.
9
Impact of hemagglutination activity and M2e immunity on conferring protection against influenza viruses.血凝活性和 M2e 免疫对预防流感病毒的影响。
Virology. 2022 Sep;574:37-46. doi: 10.1016/j.virol.2022.07.010. Epub 2022 Jul 16.
10
Highly conserved M2e and hemagglutinin epitope-based recombinant proteins induce protection against influenza virus infection.基于高度保守的 M2e 和血凝素表位的重组蛋白诱导对流感病毒感染的保护。
Microbes Infect. 2017 Dec;19(12):641-647. doi: 10.1016/j.micinf.2017.08.010. Epub 2017 Sep 10.

引用本文的文献

1
Ferritin-Based HA DNA Vaccine Outperforms Conventional Designs in Inducing Protective Immunity Against Seasonal Influenza.基于铁蛋白的HA DNA疫苗在诱导针对季节性流感的保护性免疫方面优于传统设计。
Vaccines (Basel). 2025 Jul 10;13(7):745. doi: 10.3390/vaccines13070745.
2
Chimeric hemagglutinin and M2 mRNA vaccine for broad influenza subtype protection.用于广泛流感亚型保护的嵌合血凝素和M2 mRNA疫苗。
NPJ Vaccines. 2025 Jun 5;10(1):113. doi: 10.1038/s41541-025-01178-x.
3
Dual roles of influenza B virus neuraminidase mRNA vaccine in enhancing cross-lineage protection by supplementing inactivated split vaccination.

本文引用的文献

1
Different genetic barriers for resistance to HA stem antibodies in influenza H3 and H1 viruses.流感 H3 和 H1 病毒对 HA 茎抗体的耐药性存在不同的遗传屏障。
Science. 2020 Jun 19;368(6497):1335-1340. doi: 10.1126/science.aaz5143.
2
Universal monoclonal antibody-based influenza hemagglutinin quantitative enzyme-linked immunosorbent assay.通用单克隆抗体流感血凝素定量酶联免疫吸附测定法。
Vaccine. 2019 Mar 7;37(11):1457-1466. doi: 10.1016/j.vaccine.2019.01.068. Epub 2019 Feb 11.
3
Universal Influenza Virus Vaccines That Target the Conserved Hemagglutinin Stalk and Conserved Sites in the Head Domain.
乙型流感病毒神经氨酸酶mRNA疫苗通过补充灭活裂解疫苗增强跨谱系保护的双重作用。
J Virol. 2025 May 20;99(5):e0229424. doi: 10.1128/jvi.02294-24. Epub 2025 Apr 23.
4
Design, Synthesis and Evaluation of a Candidate Fusion Epitopic Construct Vaccine Based on M2e, HA1, HA2, NA and NP Fragments of the Highly Pathogenic Avian H5N1 Influenza Virus.基于高致病性H5N1禽流感病毒M2e、HA1、HA2、NA和NP片段的候选融合表位构建疫苗的设计、合成与评价
Arch Razi Inst. 2024 Aug 1;79(4):849-856. doi: 10.32592/ARI.2024.79.4.849. eCollection 2024 Aug.
5
Addressing unexpected bacterial RNA safety concerns of E. coli produced influenza NP through CpG loaded mutant.通过负载CpG的突变体解决大肠杆菌产生的流感核蛋白意外的细菌RNA安全性问题。
NPJ Vaccines. 2025 Feb 15;10(1):32. doi: 10.1038/s41541-025-01087-z.
6
A Model H5N2 Vaccine Strain for Dual Protection Against H5N1 and H9N2 Avian Influenza Viruses.一种用于双重预防H5N1和H9N2禽流感病毒的H5N2疫苗株
Vaccines (Basel). 2024 Dec 30;13(1):22. doi: 10.3390/vaccines13010022.
7
A multi-antigen vaccinia vaccine broadly protected mice against SARS-CoV-2 and influenza A virus while also targeting SARS-CoV-1 and MERS-CoV.一种多抗原痘苗病毒疫苗可广泛保护小鼠免受严重急性呼吸综合征冠状病毒2(SARS-CoV-2)和甲型流感病毒感染,同时还能靶向严重急性呼吸综合征冠状病毒1(SARS-CoV-1)和中东呼吸综合征冠状病毒(MERS-CoV)。
Front Immunol. 2024 Nov 28;15:1473428. doi: 10.3389/fimmu.2024.1473428. eCollection 2024.
8
Delivery of dendritic cells targeting 3M2e-HA2 nanoparticles with a CpG adjuvant via lysosomal escape of Salmonella enhances protection against H9N2 avian influenza virus.通过沙门氏菌的溶酶体逃逸递送靶向3M2e-HA2纳米颗粒并带有CpG佐剂的树突状细胞可增强对H9N2禽流感病毒的保护作用。
Poult Sci. 2025 Jan;104(1):104616. doi: 10.1016/j.psj.2024.104616. Epub 2024 Dec 1.
9
Basic Properties and Development Status of Aluminum Adjuvants Used for Vaccines.用于疫苗的铝佐剂的基本特性与发展现状
Vaccines (Basel). 2024 Oct 18;12(10):1187. doi: 10.3390/vaccines12101187.
10
The self-assembled nanoparticle-based multi-epitope influenza mRNA vaccine elicits protective immunity against H1N1 and B influenza viruses in mice.基于自组装纳米颗粒的多表位流感 mRNA 疫苗在小鼠中引发针对 H1N1 和 B 型流感病毒的保护性免疫。
Front Immunol. 2024 Oct 8;15:1483720. doi: 10.3389/fimmu.2024.1483720. eCollection 2024.
针对保守的血凝素茎和头部结构域保守位点的通用流感病毒疫苗。
J Infect Dis. 2019 Apr 8;219(Suppl_1):S62-S67. doi: 10.1093/infdis/jiy711.
4
Update: Influenza Activity in the United States During the 2017-18 Season and Composition of the 2018-19 Influenza Vaccine.更新:2017-18 年度美国流感活动情况和 2018-19 年度流感疫苗成分。
MMWR Morb Mortal Wkly Rep. 2018 Jun 8;67(22):634-642. doi: 10.15585/mmwr.mm6722a4.
5
Vaccine options for influenza: thinking small.流感疫苗选择:从小处着眼。
Curr Opin Immunol. 2018 Aug;53:22-29. doi: 10.1016/j.coi.2018.03.024. Epub 2018 Apr 7.
6
Shingrix: The New Adjuvanted Recombinant Herpes Zoster Vaccine.欣格来福:新型佐剂重组带状疱疹疫苗。
Ann Pharmacother. 2018 Jul;52(7):673-680. doi: 10.1177/1060028018758431. Epub 2018 Feb 18.
7
Double-layered protein nanoparticles induce broad protection against divergent influenza A viruses.双层蛋白纳米颗粒诱导针对多种流感 A 病毒的广泛保护。
Nat Commun. 2018 Jan 24;9(1):359. doi: 10.1038/s41467-017-02725-4.
8
Protective efficacy of influenza group 2 hemagglutinin stem-fragment immunogen vaccines.流感2组血凝素茎段免疫原疫苗的保护效力
NPJ Vaccines. 2017 Dec 15;2:35. doi: 10.1038/s41541-017-0036-2. eCollection 2017.
9
Characterization of FcγRIIIA effector cells used in in vitro ADCC bioassay: Comparison of primary NK cells with engineered NK-92 and Jurkat T cells.用于体外ADCC生物测定的FcγRIIIA效应细胞的表征:原代自然杀伤细胞与工程化NK-92和Jurkat T细胞的比较。
J Immunol Methods. 2017 Feb;441:56-66. doi: 10.1016/j.jim.2016.12.002. Epub 2016 Dec 8.
10
Roles of Aluminum Hydroxide and Monophosphoryl Lipid A Adjuvants in Overcoming CD4+ T Cell Deficiency To Induce Isotype-Switched IgG Antibody Responses and Protection by T-Dependent Influenza Vaccine.氢氧化铝和单磷酰脂质A佐剂在克服CD4 + T细胞缺陷以诱导依赖T细胞的流感疫苗产生同种型转换IgG抗体反应及保护作用中的作用。
J Immunol. 2017 Jan 1;198(1):279-291. doi: 10.4049/jimmunol.1600173. Epub 2016 Nov 23.