Nie Jiaojiao, Wang Qingyu, Jin Shenghui, Yao Xin, Xu Lipeng, Chang Yaotian, Ding Fan, Li Zeyu, Sun Lulu, Shi Yuhua, Shan Yaming
National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Jilin, 130012 China.
Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences, Jilin University, Jilin, 130012 China.
Nano Res. 2023;16(5):7337-7346. doi: 10.1007/s12274-023-5395-6. Epub 2023 Feb 16.
Current seasonal influenza vaccines confer only limited coverage of virus strains due to the frequent genetic and antigenic variability of influenza virus (IV). Epitope vaccines that accurately target conserved domains provide a promising approach to increase the breadth of protection; however, poor immunogenicity greatly hinders their application. The protruding (P) domain of the norovirus (NoV), which can self-assemble into a 24-mer particle called the NoV P particle, offers an ideal antigen presentation platform. In this study, a multiepitope nanovaccine displaying influenza epitopes (HMN-PP) was constructed based on the NoV P particle nanoplatform. Large amounts of HMN-PP were easily expressed in in soluble form. Animal experiments showed that the adjuvanted HMN-PP nanovaccine induced epitope-specific antibodies and haemagglutinin (HA)-specific neutralizing antibodies, and the antibodies could persist for at least three months after the last immunization. Furthermore, HMN-PP induced matrix protein 2 extracellular domain (M2e)-specific antibody-dependent cell-mediated cytotoxicity, CD4 and CD8 T-cell responses, and a nucleoprotein (NP)-specific cytotoxic T lymphocyte (CTL) response. These results indicated that the combination of a multiepitope vaccine and self-assembled NoV P particles may be an ideal and effective vaccine strategy for highly variable viruses such as IV and SARS-CoV-2.
Supplementary material is available in the online version of this article at 10.1007/s12274-023-5395-6.
由于流感病毒（IV）频繁的基因和抗原变异，目前的季节性流感疫苗对病毒株的覆盖范围有限。准确靶向保守结构域的表位疫苗为扩大保护范围提供了一种有前景的方法；然而，免疫原性差极大地阻碍了它们的应用。诺如病毒（NoV）的突出（P）结构域可自组装成一种称为NoV P颗粒的24聚体颗粒，提供了一个理想的抗原呈递平台。在本研究中，基于NoV P颗粒纳米平台构建了一种展示流感表位的多表位纳米疫苗（HMN-PP）。大量的HMN-PP易于以可溶性形式表达。动物实验表明，佐剂化的HMN-PP纳米疫苗诱导了表位特异性抗体和血凝素（HA）特异性中和抗体，并且这些抗体在最后一次免疫后至少可持续三个月。此外，HMN-PP诱导了基质蛋白2胞外结构域（M2e）特异性抗体依赖性细胞介导的细胞毒性、CD4和CD8 T细胞反应以及核蛋白（NP）特异性细胞毒性T淋巴细胞（CTL）反应。这些结果表明，多表位疫苗与自组装的NoV P颗粒的组合可能是针对IV和SARS-CoV-2等高变异性病毒的理想且有效的疫苗策略。
补充材料可在本文的在线版本中获取，链接为10.1007/s12274-023-5395-6。
