1. Academic Validation
  2. A broad-spectrum multiepitope vaccine against seasonal influenza A and B viruses in mice

A broad-spectrum multiepitope vaccine against seasonal influenza A and B viruses in mice

  • EBioMedicine. 2024 Aug:106:105269. doi: 10.1016/j.ebiom.2024.105269.
Lifang Yuan 1 Shengze Zhang 2 Rongjun Bi 3 Xuejie Liu 4 Zirong Han 5 Minchao Li 6 Xinzhong Liao 7 Ting Xie 8 Shaohui Bai 9 Qian Xie 10 Chuming Luo 11 Ying Jiang 12 Jianhui Yuan 13 Huanle Luo 14 Huacheng Yan 15 Caijun Sun 16 Yuelong Shu 17
Affiliations

Affiliations

  • 1 School of Public Health (Shenzhen), Shenzhen Key Laboratory of Pathogenic Microbes and Biosafetuy, Shenzhen Campus of Sun Yat-sen University, Shenzhen, 518107, PR China. Electronic address: yuanlf6@mail2.sysu.edu.cn.
  • 2 School of Public Health (Shenzhen), Shenzhen Key Laboratory of Pathogenic Microbes and Biosafetuy, Shenzhen Campus of Sun Yat-sen University, Shenzhen, 518107, PR China. Electronic address: zhangshz5@mail2.sysu.edu.cn.
  • 3 School of Public Health (Shenzhen), Shenzhen Key Laboratory of Pathogenic Microbes and Biosafetuy, Shenzhen Campus of Sun Yat-sen University, Shenzhen, 518107, PR China. Electronic address: birj@mail2.sysu.edu.cn.
  • 4 School of Public Health (Shenzhen), Shenzhen Key Laboratory of Pathogenic Microbes and Biosafetuy, Shenzhen Campus of Sun Yat-sen University, Shenzhen, 518107, PR China. Electronic address: liuxj89@mail2.sysu.edu.cn.
  • 5 School of Public Health (Shenzhen), Shenzhen Key Laboratory of Pathogenic Microbes and Biosafetuy, Shenzhen Campus of Sun Yat-sen University, Shenzhen, 518107, PR China. Electronic address: hanzr@mail2.sysu.edu.cn.
  • 6 School of Public Health (Shenzhen), Shenzhen Key Laboratory of Pathogenic Microbes and Biosafetuy, Shenzhen Campus of Sun Yat-sen University, Shenzhen, 518107, PR China. Electronic address: liminchao@mail2.sysu.edu.cn.
  • 7 School of Public Health (Shenzhen), Shenzhen Key Laboratory of Pathogenic Microbes and Biosafetuy, Shenzhen Campus of Sun Yat-sen University, Shenzhen, 518107, PR China. Electronic address: liaoxzh8@mail2.sysu.edu.cn.
  • 8 School of Public Health (Shenzhen), Shenzhen Key Laboratory of Pathogenic Microbes and Biosafetuy, Shenzhen Campus of Sun Yat-sen University, Shenzhen, 518107, PR China. Electronic address: xiet27@mail2.sysu.edu.cn.
  • 9 School of Public Health (Shenzhen), Shenzhen Key Laboratory of Pathogenic Microbes and Biosafetuy, Shenzhen Campus of Sun Yat-sen University, Shenzhen, 518107, PR China. Electronic address: baishh7@mail2.sysu.edu.cn.
  • 10 School of Public Health (Shenzhen), Shenzhen Key Laboratory of Pathogenic Microbes and Biosafetuy, Shenzhen Campus of Sun Yat-sen University, Shenzhen, 518107, PR China. Electronic address: xieq59@mail.sysu.edu.cn.
  • 11 School of Public Health (Shenzhen), Shenzhen Key Laboratory of Pathogenic Microbes and Biosafetuy, Shenzhen Campus of Sun Yat-sen University, Shenzhen, 518107, PR China. Electronic address: luochm7@mail.sysu.edu.cn.
  • 12 Shenzhen Nanshan Centre for Disease Control and Prevention, Shenzhen, 518054, PR China. Electronic address: wangtiedan0111@126.com.
  • 13 Shenzhen Nanshan Centre for Disease Control and Prevention, Shenzhen, 518054, PR China. Electronic address: sncdcyjh@szns.gov.cn.
  • 14 School of Public Health (Shenzhen), Shenzhen Key Laboratory of Pathogenic Microbes and Biosafetuy, Shenzhen Campus of Sun Yat-sen University, Shenzhen, 518107, PR China; Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, 510080, PR China. Electronic address: luohle@mail.sysu.edu.cn.
  • 15 Centre for Disease Control and Prevention of Southern Military Theatre, 510610, Guangzhou, PR China. Electronic address: watshing@126.com.
  • 16 School of Public Health (Shenzhen), Shenzhen Key Laboratory of Pathogenic Microbes and Biosafetuy, Shenzhen Campus of Sun Yat-sen University, Shenzhen, 518107, PR China; Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou, 510080, PR China. Electronic address: suncaijun@mail.sysu.edu.cn.
  • 17 School of Public Health (Shenzhen), Shenzhen Key Laboratory of Pathogenic Microbes and Biosafetuy, Shenzhen Campus of Sun Yat-sen University, Shenzhen, 518107, PR China; Key Laboratory of Pathogen Infection Prevention and Control (MOE), State Key Laboratory of Respiratory Health and Multimorbidity, National Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 102629, PR China. Electronic address: shuylong@mail.sysu.edu.cn.
Abstract

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.

Keywords

Broad-spectrum vaccine; Influenza; Multiepitope; Peptide; Peptide-based vaccine.

Figures
Products