{"title":"针对小鼠季节性甲型和乙型流感病毒的广谱多位面疫苗。","authors":"Lifang Yuan, Shengze Zhang, Rongjun Bi, Xuejie Liu, Zirong Han, Minchao Li, Xinzhong Liao, Ting Xie, Shaohui Bai, Qian Xie, Chuming Luo, Ying Jiang, Jianhui Yuan, Huanle Luo, Huacheng Yan, Caijun Sun, Yuelong Shu","doi":"10.1016/j.ebiom.2024.105269","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Influenza viruses pose a persistent threat to global public health, necessitating the development of innovative and broadly effective vaccines.</p><p><strong>Methods: </strong>This study focuses on a multiepitope vaccine (MEV) designed to provide broad-spectrum protection against different influenza viruses. The MEV, containing 19 B-cell linear epitopes, 7 CD4<sup>+</sup> T cells, and 11 CD8<sup>+</sup> T cells epitopes identified through enzyme-linked immunospot assay (ELISPOT) in influenza viruses infected mice, was administered through a regimen of two doses of DNA vaccine followed by one dose of a protein vaccine in C57BL/6 female mice.</p><p><strong>Findings: </strong>Upon lethal challenge with both seasonal circulating strains (H1N1, H3N2, BV, and BY) and historical strains (H1N1-PR8 and H3N2-X31), MEV demonstrated substantial protection against different influenza seasonal strains, with partial efficacy against historical strains. Notably, the increased germinal centre B cells and antibody-secreting cells, along with robust T cell immune responses, highlighted the comprehensive immune defence elicited by MEV. Elevated hemagglutinin inhibition antibody was also observed against seasonal circulating and historical strains. Additionally, mice vaccinated with MEV exhibited significantly lower counts of inflammatory cells in the lungs compared to negative control groups.</p><p><strong>Interpretation: </strong>Our results demonstrated the efficacy of a broad-spectrum MEV against influenza viruses in mice. Conducting long-term studies to evaluate the durability of MEV-induced immune responses and explore its potential application in diverse populations will offer valuable insights for the continued advancement of this promising vaccine.</p><p><strong>Funding: </strong>Funding bodies are described in the Acknowledgments section.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":null,"pages":null},"PeriodicalIF":9.7000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11350506/pdf/","citationCount":"0","resultStr":"{\"title\":\"A broad-spectrum multiepitope vaccine against seasonal influenza A and B viruses in mice.\",\"authors\":\"Lifang Yuan, Shengze Zhang, Rongjun Bi, Xuejie Liu, Zirong Han, Minchao Li, Xinzhong Liao, Ting Xie, Shaohui Bai, Qian Xie, Chuming Luo, Ying Jiang, Jianhui Yuan, Huanle Luo, Huacheng Yan, Caijun Sun, Yuelong Shu\",\"doi\":\"10.1016/j.ebiom.2024.105269\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Influenza viruses pose a persistent threat to global public health, necessitating the development of innovative and broadly effective vaccines.</p><p><strong>Methods: </strong>This study focuses on a multiepitope vaccine (MEV) designed to provide broad-spectrum protection against different influenza viruses. The MEV, containing 19 B-cell linear epitopes, 7 CD4<sup>+</sup> T cells, and 11 CD8<sup>+</sup> T cells epitopes identified through enzyme-linked immunospot assay (ELISPOT) in influenza viruses infected mice, was administered through a regimen of two doses of DNA vaccine followed by one dose of a protein vaccine in C57BL/6 female mice.</p><p><strong>Findings: </strong>Upon lethal challenge with both seasonal circulating strains (H1N1, H3N2, BV, and BY) and historical strains (H1N1-PR8 and H3N2-X31), MEV demonstrated substantial protection against different influenza seasonal strains, with partial efficacy against historical strains. Notably, the increased germinal centre B cells and antibody-secreting cells, along with robust T cell immune responses, highlighted the comprehensive immune defence elicited by MEV. Elevated hemagglutinin inhibition antibody was also observed against seasonal circulating and historical strains. Additionally, mice vaccinated with MEV exhibited significantly lower counts of inflammatory cells in the lungs compared to negative control groups.</p><p><strong>Interpretation: </strong>Our results demonstrated the efficacy of a broad-spectrum MEV against influenza viruses in mice. Conducting long-term studies to evaluate the durability of MEV-induced immune responses and explore its potential application in diverse populations will offer valuable insights for the continued advancement of this promising vaccine.</p><p><strong>Funding: </strong>Funding bodies are described in the Acknowledgments section.</p>\",\"PeriodicalId\":11494,\"journal\":{\"name\":\"EBioMedicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":9.7000,\"publicationDate\":\"2024-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11350506/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"EBioMedicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.ebiom.2024.105269\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/8/6 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"EBioMedicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ebiom.2024.105269","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/6 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
摘要
背景:流感病毒对全球公共卫生构成持续威胁,因此有必要开发创新且广泛有效的疫苗:本研究的重点是一种多表位疫苗(MEV),旨在提供针对不同流感病毒的广谱保护。MEV包含19个B细胞线性表位、7个CD4+T细胞表位和11个CD8+T细胞表位,这些表位是通过酶联免疫吸附试验(ELISPOT)在感染流感病毒的小鼠体内鉴定出来的:研究结果:在受到季节性流行毒株(H1N1、H3N2、BV 和 BY)和历史毒株(H1N1-PR8 和 H3N2-X31)的致命挑战时,MEV 对不同的季节性流感毒株有很强的保护作用,对历史毒株有部分疗效。值得注意的是,生殖中心 B 细胞和抗体分泌细胞的增加,以及强大的 T 细胞免疫反应,凸显了 MEV 所引发的全面免疫防御。针对季节性流行毒株和历史毒株的血凝素抑制抗体也有所升高。此外,与阴性对照组相比,接种了 MEV 疫苗的小鼠肺部炎症细胞数量明显减少:我们的研究结果证明了广谱MEV对小鼠流感病毒的疗效。开展长期研究以评估MEV诱导的免疫反应的持久性,并探索其在不同人群中的潜在应用,将为这种前景广阔的疫苗的持续发展提供有价值的见解:资助机构见致谢部分。
A broad-spectrum multiepitope vaccine against seasonal influenza A and B viruses in mice.
Background: Influenza viruses pose a persistent threat to global public health, necessitating the development of innovative and broadly effective vaccines.
Methods: This study focuses on a multiepitope vaccine (MEV) designed to provide broad-spectrum protection against different influenza viruses. The MEV, containing 19 B-cell linear epitopes, 7 CD4+ T cells, and 11 CD8+ T cells epitopes identified through enzyme-linked immunospot assay (ELISPOT) in influenza viruses infected mice, was administered through a regimen of two doses of DNA vaccine followed by one dose of a protein vaccine in C57BL/6 female mice.
Findings: Upon lethal challenge with both seasonal circulating strains (H1N1, H3N2, BV, and BY) and historical strains (H1N1-PR8 and H3N2-X31), MEV demonstrated substantial protection against different influenza seasonal strains, with partial efficacy against historical strains. Notably, the increased germinal centre B cells and antibody-secreting cells, along with robust T cell immune responses, highlighted the comprehensive immune defence elicited by MEV. Elevated hemagglutinin inhibition antibody was also observed against seasonal circulating and historical strains. Additionally, mice vaccinated with MEV exhibited significantly lower counts of inflammatory cells in the lungs compared to negative control groups.
Interpretation: Our results demonstrated the efficacy of a broad-spectrum MEV against influenza viruses in mice. Conducting long-term studies to evaluate the durability of MEV-induced immune responses and explore its potential application in diverse populations will offer valuable insights for the continued advancement of this promising vaccine.
Funding: Funding bodies are described in the Acknowledgments section.
EBioMedicineBiochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology
CiteScore
17.70
自引率
0.90%
发文量
579
审稿时长
5 weeks
期刊介绍:
eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.