School of Public Health (Shenzhen), Shenzhen Key Laboratory of Pathogenic Microbes and Biosafetuy, Shenzhen Campus of Sun Yat-sen University, Shenzhen, 518107, PR China.
Shenzhen Nanshan Centre for Disease Control and Prevention, Shenzhen, 518054, PR China.
EBioMedicine. 2024 Aug;106:105269. doi: 10.1016/j.ebiom.2024.105269. Epub 2024 Aug 6.
Influenza viruses pose a persistent threat to global public health, necessitating the development of innovative and broadly effective vaccines.
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.
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.
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 bodies are described in the Acknowledgments section.
流感病毒对全球公共卫生构成持续威胁，因此需要开发创新且广泛有效的疫苗。
本研究专注于一种多表位疫苗（MEV），旨在针对不同的流感病毒提供广谱保护。该 MEV 包含通过酶联免疫斑点法（ELISPOT）在感染流感病毒的小鼠中鉴定出的 19 个 B 细胞线性表位、7 个 CD4 T 细胞和 11 个 CD8 T 细胞表位，通过两剂 DNA 疫苗和一剂蛋白疫苗的方案在 C57BL/6 雌性小鼠中进行给药。
在致死性挑战中，MEV 对季节性流行株（H1N1、H3N2、BV 和 BY）和历史株（H1N1-PR8 和 H3N2-X31）均表现出显著的保护作用，对历史株具有部分疗效。值得注意的是，增加的生发中心 B 细胞和抗体分泌细胞以及强大的 T 细胞免疫反应突出了 MEV 引发的全面免疫防御。还观察到针对季节性流行株和历史株的血凝素抑制抗体升高。此外，与阴性对照组相比，接种 MEV 的小鼠肺部的炎症细胞计数明显降低。
我们的结果证明了广谱 MEV 在小鼠中对抗流感病毒的功效。进行长期研究以评估 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，将为推进这种有前途的疫苗提供有价值的见解。
资助机构在致谢部分中描述。
