The self-assembled nanoparticle-based multi-epitope influenza mRNA vaccine elicits protective immunity against H1N1 and B influenza viruses in mice

文献类型： 外文期刊

第一作者： Di, Yaxin

作者： Di, Yaxin;Jin, Ningyi;Di, Yaxin;Ren, Zilin;Yang, Songhui;Zhuang, Xinyu;Jin, Ningyi;Tian, Mingyao;Zhang, Chenchao;Jiang, Renyue;Xu, Zhiqiang;Tang, Jiafeng;Wang, Ziliang;Yu, Tong;Yu, Ziping;Zhang, Tong;Jin, Ningyi

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关键词： influenza virus; multivalent epitopes; nanoparticle; mRNA vaccines; immunogenicity

期刊名称：FRONTIERS IN IMMUNOLOGY （ 影响因子：5.9； 五年影响因子：6.8 ）

ISSN： 1664-3224

年卷期： 2024 年 15 卷

页码：

收录情况： SCI

摘要： Introduction The influenza virus is recognized as the primary cause of human respiratory diseases, with the current influenza vaccine primarily offering strain-specific immunity and limited protection against drifting strains. Considering this, the development of a broad-spectrum influenza vaccine capable of inducing effective immunity is considered the future direction in combating influenza.Methods The present study proposes a novel mRNA-based multi-epitope influenza vaccine, which combines three conserved antigens derived from the influenza A virus. The antigens consist of M2 ion channel's extracellular domain (M2e), the conserved epitope of located in HA2 of hemagglutinin (H1, H3, B), and HA1 of hemagglutinin. At the same time, trimeric sequences and ferritin were conjugated separately to investigate the immune effects of antigen multivalent presentation.Results Immunization studies conducted on C57BL/6 mice with these vaccines revealed that they can elicit both humoral immunity and CD4+ and CD8+ T cell responses, which collectively contribute to enhancing cross-protective effects. The virus challenge results showed that vaccinated groups had significantly reduced lung damage, lower viral loads in the lungs, nasal turbinates, and trachea, as well as decreased levels of pro-inflammatory cytokines.Conclusion These findings clearly demonstrate the wide range of protective effects provided by these vaccines against H1N1 and B influenza viruses. The present finding highlights the potential of mRNA-based influenza vaccines encoding conserved proteins as a promising strategy for eliciting broad-spectrum protective humoral and cellular immunity against H1N1 and B influenza viruses.

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