Monophosphoryl lipid A-adjuvanted nucleoprotein-neuraminidase nanoparticles improve immune protection against divergent influenza viruses

IF 4.7 4区 医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Ye Wang PhD , Chunhong Dong PhD , Yao Ma PhD , Wandi Zhu PhD , Harvinder Singh Gill PhD , Timothy L. Denning PhD , Sang-Moo Kang PhD , Bao-Zhong Wang PhD
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引用次数: 2

Abstract

Universal influenza vaccines are urgently needed to prevent recurrent influenza epidemics and inevitable pandemics. We generated double-layered protein nanoparticles incorporating two conserved influenza antigens—nucleoprotein and neuraminidase—through a two-step desolvation-crosslinking method. These protein nanoparticles displayed immunostimulatory properties to antigen-presenting cells by promoting inflammatory cytokine (IL-6 and TNF-α) secretion from JAWS II dendric cells. The nanoparticle immunization induced significant antigen-specific humoral and cellular responses, including antigen-binding and neutralizing antibodies, antibody- and cytokine (IFN-γ and IL-4)-secreting cells, and NP147155 tetramer-specific cytotoxic T lymphocyte (CTL) responses. Co-administration of monophosphoryl lipid A (MPLA, a toll-like receptor 4 agonist) with the protein nanoparticles further improved immune responses and conferred heterologous and heterosubtypic influenza protection. The MPLA-adjuvanted nanoparticles reduced lung inflammation post-infection. The results demonstrated that the combination of MPLA and conserved protein nanoparticles could be developed into an improved universal influenza vaccine strategy.

Abstract Image

单磷酰脂质a佐剂核蛋白-神经氨酸酶纳米颗粒提高对不同流感病毒的免疫保护
迫切需要通用流感疫苗,以防止流感复发和不可避免的大流行。我们通过两步脱溶-交联方法制备了包含两种保守的流感抗原-核蛋白和神经氨酸酶-的双层蛋白质纳米颗粒。这些蛋白质纳米颗粒通过促进JAWS II树突细胞分泌炎症细胞因子(IL-6和TNF-α),对抗原提呈细胞表现出免疫刺激特性。纳米颗粒免疫诱导了显著的抗原特异性体液和细胞反应,包括抗原结合和中和抗体,抗体和细胞因子(IFN-γ和IL-4)分泌细胞,以及NP147-155四聚体特异性细胞毒性T淋巴细胞(CTL)反应。单磷酰脂质A (MPLA,一种toll样受体4激动剂)与蛋白质纳米颗粒共同施用进一步改善了免疫应答,并赋予异源和异亚型流感保护作用。mpla佐剂纳米颗粒减少了感染后的肺部炎症。结果表明,MPLA与保守蛋白纳米颗粒的结合可以发展成为一种改进的通用流感疫苗策略。
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来源期刊
CiteScore
8.10
自引率
3.60%
发文量
104
审稿时长
4.6 months
期刊介绍: Nanomedicine: Nanotechnology, Biology and Medicine (NBM) is an international, peer-reviewed journal presenting novel, significant, and interdisciplinary theoretical and experimental results related to nanoscience and nanotechnology in the life and health sciences. Content includes basic, translational, and clinical research addressing diagnosis, treatment, monitoring, prediction, and prevention of diseases.
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