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一种用于设计经典猪瘟疫苗的自组装铁蛋白纳米平台:强效中和抗体的诱导

A Self-Assembling Ferritin Nanoplatform for Designing Classical Swine Fever Vaccine: Elicitation of Potent Neutralizing Antibody.

作者信息

Zhao Zekai, Chen Xinghua, Chen Yibao, Li Hui, Fang Kui, Chen Huanchun, Li Xiangmin, Qian Ping

机构信息

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China.

College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.

出版信息

Vaccines (Basel). 2021 Jan 13;9(1):45. doi: 10.3390/vaccines9010045.

Abstract

Protein-based self-assembling nanoplatforms exhibit superior immunogenicity compared with soluble antigens. Here, we present a comprehensive vaccine strategy for displaying classical swine fever virus (CSFV) E2 glycoprotein on the surface of ferritin (fe) nanocages. An E2-specific blocking antibody assay showed that the blocking rates in E2-fe/Gel02 (84.3%) and a half-dose cohort of E2-fe/Gel02 (81.9%) were significantly higher ( < 0.05) than that in a ferritin-free cohort of E2/Gel02 (62.7%) at 21 days post immunization (dpi) in vivo. Furthermore, quantitation of neutralizing potency revealed that a highly significant difference ( < 0.001) was observed between the E2-fe/Gel02 cohort (1:32, equivalent to live-attenuated strain C at 1:32) and the E2/Gel02 cohort (1:4) at 21 dpi. Moreover, the innate immune cytokines of IL-4 and IFN-γ activated by the half-dose (20 μg) cohort of E2-fe/Gel02 were equivalent to those elicited by the full dose (40 μg) of purified E2 in the E2/Gel02 cohort at most time points. In conclusion, we successfully obtained an antigen-displaying E2-ferritin nanoplatform and confirmed high ferritin-assisted humoral and cellular immunities. Our results provided a novel paradigm of self-assembling nanovaccine development for the defense and elimination of potentially pandemic infectious viral pathogens.

摘要

与可溶性抗原相比,基于蛋白质的自组装纳米平台具有更强的免疫原性。在此,我们提出了一种全面的疫苗策略,用于在铁蛋白(Fe)纳米笼表面展示经典猪瘟病毒(CSFV)E2糖蛋白。E2特异性阻断抗体检测表明,在体内免疫后21天(dpi),E2-fe/Gel02组(84.3%)和半剂量E2-fe/Gel02组(81.9%)的阻断率显著高于无铁蛋白的E2/Gel02组(62.7%)(P<0.05)。此外,中和效力定量显示,在21 dpi时,E2-fe/Gel02组(1:32,相当于减毒活疫苗株C的1:32)和E2/Gel02组(1:4)之间存在高度显著差异(P<0.001)。此外,在大多数时间点,半剂量(20μg)E2-fe/Gel02组激活的IL-4和IFN-γ先天免疫细胞因子与E2/Gel02组中全剂量(40μg)纯化E2引发的细胞因子相当。总之,我们成功获得了展示抗原的E2-铁蛋白纳米平台,并证实了铁蛋白辅助的高效体液免疫和细胞免疫。我们的结果为防御和消除潜在的大流行性传染性病毒病原体提供了一种自组装纳米疫苗开发的新范例。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ede4/7828615/594b0f5f18f2/vaccines-09-00045-g001.jpg

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