多室疫苗颗粒可引发针对蛋白抗原的强烈免疫激活，并保护小鼠免受埃博拉病毒感染。
Multilamellar Vaccine Particle Elicits Potent Immune Activation with Protein Antigens and Protects Mice against Ebola Virus Infection.
机构信息
Department of Pharmaceutical Sciences , University of Michigan , Ann Arbor , Michigan 48109 , United States.
Biointerfaces Institute , University of Michigan , Ann Arbor , Michigan 48109 , United States.
出版信息
ACS Nano. 2019 Oct 22;13(10):11087-11096. doi: 10.1021/acsnano.9b03660. Epub 2019 Sep 12.
Abstract
Recent outbreaks of emerging infectious diseases, such as Ebola virus disease (EVD), highlight the urgent need to develop effective countermeasures, including prophylactic vaccines. Subunit proteins derived from pathogens provide a safe source of antigens for vaccination, but they are often limited by their low immunogenicity. We have developed a multilamellar vaccine particle (MVP) system composed of lipid-hyaluronic acid multi-cross-linked hybrid nanoparticles for vaccination with protein antigens and demonstrate their efficacy against Ebola virus (EBOV) exposure. MVPs efficiently accumulated in dendritic cells and promote antigen processing. Mice immunized with MVPs elicited robust and long-lasting antigen-specific CD8 and CD4 T cell immune responses as well as humoral immunity. A single-dose vaccination with MVPs delivering EBOV glycoprotein achieved an 80% protection rate against lethal EBOV infection. These results suggest that MVPs offer a promising platform for improving recombinant protein-based vaccine approaches.
摘要
最近爆发的新兴传染病，如埃博拉病毒病（EVD），突出表明迫切需要开发有效的对策，包括预防性疫苗。源自病原体的亚单位蛋白为疫苗接种提供了安全的抗原来源，但它们通常受到免疫原性低的限制。我们开发了一种由脂质-透明质酸多交联混合纳米颗粒组成的多层疫苗颗粒（MVP）系统，用于蛋白抗原的疫苗接种，并证明了它们在对抗埃博拉病毒（EBOV）暴露方面的功效。MVPs 能够有效地在树突状细胞中积累，并促进抗原处理。用 MVPs 免疫的小鼠引发了强烈且持久的抗原特异性 CD8 和 CD4 T 细胞免疫应答以及体液免疫。单次接种 MVP 递送的 EBOV 糖蛋白可实现 80%的抗致死性 EBOV 感染保护率。这些结果表明，MVPs 为改进基于重组蛋白的疫苗方法提供了一个有前途的平台。
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