Multilamellar Vaccine Particle Elicits Potent Immune Activation with Protein Antigens and Protects Mice against Ebola Virus Infection
Multilamellar Vaccine Particle Elicits Potent Immune Activation with Protein Antigens and Protects Mice against Ebola Virus Infection
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DOI：
10.1021/acsnano.9b03660
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发表时间：
2019-10-01
期刊：
影响因子：
17.1
通讯作者：
Moon, James J.
中科院分区：
文献类型：
--
作者：
Fan, Yuchen;Stronsky, Sabrina M.;Moon, James J.
最近爆发的新发传染病，如埃博拉病毒病，突出表明迫切需要制定有效的对策，包括预防性疫苗。来自病原体的亚基蛋白为疫苗接种提供了一种安全的抗原来源，但它们往往受到低免疫原性的限制。我们开发了一种由脂质-透明质酸多交联杂交纳米颗粒组成的多层疫苗颗粒（MVP）系统，用于蛋白质抗原的疫苗接种，并证明了它们对埃博拉病毒（EBOV）暴露的有效性。mvp有效地在树突状细胞中积累并促进抗原加工。用MVPs免疫小鼠，可引起稳健且持久的抗原特异性CD8（+）和CD4(+) T细胞免疫反应以及体液免疫。单剂量接种提供EBOV糖蛋白的MVPs疫苗，对EBOV致命感染的保护率达到80%。这些结果表明，mvp为改进基于重组蛋白的疫苗方法提供了一个有希望的平台。
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.