Double-Layered M2e-NA Protein Nanoparticle Immunization Induces Broad Cross-Protection against Different Influenza Viruses in Mice.,Advanced Healthcare Materials

当前位置： X-MOL 学术 › Adv. Healthcare Mater. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Double-Layered M2e-NA Protein Nanoparticle Immunization Induces Broad Cross-Protection against Different Influenza Viruses in Mice.
Advanced Healthcare Materials ( IF 10.0 ) Pub Date : 2019-12-15 , DOI: 10.1002/adhm.201901176
Ye Wang ₁ , Lei Deng ₁ , Gilbert X Gonzalez ₁ , Latika Luthra ₁ , Chunhong Dong ₁ , Yao Ma ₁ , Jun Zou ₁ , Sang-Moo Kang ₁ , Bao-Zhong Wang ₁

Affiliation

The development of a universal influenza vaccine is an ideal strategy to eliminate public health threats from influenza epidemics and pandemics. This ultimate goal is restricted by the low immunogenicity of conserved influenza epitopes. Layered protein nanoparticles composed of well-designed conserved influenza structures have shown improved immunogenicity with new physical and biochemical features. Herein, structure-stabilized influenza matrix protein 2 ectodomain (M2e) and M2e-neuraminidase fusion (M2e-NA) recombinant proteins are generated and M2e protein nanoparticles and double-layered M2e-NA protein nanoparticles are produced by ethanol desolvation and chemical crosslinking. Immunizations with these protein nanoparticles induce immune protection against different viruses of homologous and heterosubtypic NA in mice. Double-layered M2e-NA protein nanoparticles induce higher levels of humoral and cellular responses compared with their comprising protein mixture or M2e nanoparticles. Strong cytotoxic T cell responses are induced in the layered M2e-NA protein nanoparticle groups. Antibody responses contribute to the heterosubtypic NA immune protection. The protective immunity is long lasting. These results demonstrate that double-layered protein nanoparticles containing structure-stabilized M2e and NA can be developed into a universal influenza vaccine or a synergistic component of such vaccines. Layered protein nanoparticles can be a general vaccine platform for different pathogens.

中文翻译：

双层 M2e-NA 蛋白纳米颗粒免疫可在小鼠体内诱导针对不同流感病毒的广泛交叉保护。

开发通用流感疫苗是消除流感流行和大流行对公共卫生威胁的理想策略。这一最终目标受到保守流感表位的低免疫原性的限制。由精心设计的保守流感结构组成的层状蛋白质纳米颗粒显示出具有新的物理和生化特征的改进的免疫原性。在此，产生结构稳定的流感基质蛋白2胞外域（M2e）和M2e-神经氨酸酶融合（M2e-NA）重组蛋白，并通过乙醇去溶剂化和化学交联产生M2e蛋白纳米颗粒和双层M2e-NA蛋白纳米颗粒。使用这些蛋白质纳米颗粒进行免疫可以在小鼠体内诱导针对同源和异亚型 NA 的不同病毒的免疫保护。与包含蛋白质混合物或M2e纳米粒子的双层M2e-NA蛋白质纳米粒子相比，双层M2e-NA蛋白质纳米粒子诱导更高水平的体液和细胞反应。分层的 M2e-NA 蛋白纳米颗粒组会诱导强烈的细胞毒性 T 细胞反应。抗体反应有助于异亚型 NA 免疫保护。保护性免疫力是持久的。这些结果表明，含有结构稳定的M2e和NA的双层蛋白纳米颗粒可以开发成通用流感疫苗或此类疫苗的协同成分。层状蛋白质纳米颗粒可以成为针对不同病原体的通用疫苗平台。

更新日期：2020-01-23

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11