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基于自组装纳米颗粒的多表位流感 mRNA 疫苗在小鼠中引发针对 H1N1 和 B 型流感病毒的保护性免疫。

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

机构信息

College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.

Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, State Key Laboratory of Pathogen and Biosecurity, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Changchun, China.

出版信息

Front Immunol. 2024 Oct 8;15:1483720. doi: 10.3389/fimmu.2024.1483720. eCollection 2024.

Abstract

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.

摘要

简介

流感病毒被认为是人类呼吸道疾病的主要病原体,目前的流感疫苗主要提供针对特定毒株的免疫保护,对漂移株的保护作用有限。因此,开发一种能够诱导有效免疫的广谱流感疫苗被认为是未来防治流感的方向。

方法

本研究提出了一种新型的基于 mRNA 的多表位流感疫苗,该疫苗结合了三种来自流感 A 病毒的保守抗原。这些抗原包括 M2 离子通道的胞外域(M2e)、血凝素(H1、H3、B)中位于 HA2 保守表位和血凝素的 HA1。同时,将三聚体序列和铁蛋白分别连接,以研究抗原多价呈现的免疫效果。

结果

在 C57BL/6 小鼠上进行的免疫研究表明,这些疫苗能够引发体液免疫和 CD4 和 CD8 T 细胞反应,共同增强交叉保护作用。病毒攻击结果表明,接种疫苗的组肺部损伤明显减轻,肺部、鼻甲骨和气管中的病毒载量降低,促炎细胞因子水平降低。

结论

这些发现清楚地表明,这些疫苗对 H1N1 和 B 型流感病毒具有广泛的保护作用。本研究结果强调了编码保守蛋白的基于 mRNA 的流感疫苗作为一种有前途的策略,可诱导针对 H1N1 和 B 型流感病毒的广谱保护性体液和细胞免疫。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/affe/11497263/d6709ec6f011/fimmu-15-1483720-g001.jpg

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