A broad-spectrum multiepitope vaccine against seasonal influenza A and B viruses in mice
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
Abstract
BACKGROUND: Influenza viruses pose a persistent threat to global public health, necessitating the development of innovative and broadly effective vaccines. METHODS: 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.