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构象稳定的犬瘟热病毒血凝素纳米颗粒具有高度免疫原性,并能诱导强烈的免疫反应。

Nanoparticles of conformation-stabilized canine distemper virus hemagglutinin are highly immunogenic and induce robust immunity.

机构信息

Medical School of Jiaxing University, Jiahang Road 118#, Nanhu District, Jiaxing City, Zhejiang Province, 314001, People's Republic of China.

Military Veterinary Research Institute of Academy of Military Medical Sciences, Changchun, 130122, People's Republic of China.

出版信息

Virol J. 2021 Nov 22;18(1):229. doi: 10.1186/s12985-021-01702-0.

Abstract

BACKGROUND

Canine distemper virus (CDV) infection of ferrets, dogs, and giant pandas causes an acute systemic disease involving multiple organ systems, including the respiratory tract, lymphoid system, and central nervous system. In this study, we tested a new candidate CDV vaccine-CDV nanoparticles-based on hemagglutinin protein.

METHODS

The nanoparticles were generated from conformation-stabilized CDV hemagglutinin tetramers. Immune responses against CDV were evaluated in mice. Immunization was initiated 6 weeks after birth and boosted two times with 4-week intervals. The blood and mucosal samples were collected 2 weeks after each immunization.

RESULTS

Vaccination with CDV nanoparticles elicited high levels of IgG antibody titers in mice (approximately sevenfold to eightfold higher than that obtained with soluble CDV H protein) and mucosal immune responses and developed increased CDV-specific neutralizing antibody. The mice that received nanoparticles showed significantly higher IFN-γ- and IL-4-secreting cell population in the spleen and lymph node compared with mice immunized with soluble H protein. The co-stimulatory molecular expression of CD80 and CD86 on the surface of DCs was also upregulated.

CONCLUSION

The results demonstrate that self-assembly into nanoparticles can increase the immunogenicity of vaccine antigens, and nanoparticles assembled from conformation-stabilized CDV H protein can serve as a new CDV vaccine.

摘要

背景

犬瘟热病毒(CDV)感染雪貂、犬和大熊猫会导致涉及多个器官系统的急性全身疾病,包括呼吸道、淋巴系统和中枢神经系统。在本研究中,我们测试了一种新型犬瘟热候选疫苗 - 基于血凝素蛋白的犬瘟热纳米颗粒疫苗。

方法

纳米颗粒由构象稳定的犬瘟热血凝素四聚体生成。在小鼠中评估了针对 CDV 的免疫反应。免疫接种在出生后 6 周开始,每隔 4 周加强两次。每次免疫接种后 2 周采集血液和粘膜样本。

结果

用 CDV 纳米颗粒给小鼠接种可引起高水平的 IgG 抗体滴度(比可溶性 CDV H 蛋白高约七到八倍)和粘膜免疫反应,并产生更高的 CDV 特异性中和抗体。与用可溶性 H 蛋白免疫的小鼠相比,接受纳米颗粒的小鼠在脾脏和淋巴结中产生 IFN-γ 和 IL-4 分泌细胞群的水平明显更高。树突状细胞表面的共刺激分子 CD80 和 CD86 的表达也上调。

结论

结果表明,自组装成纳米颗粒可以提高疫苗抗原的免疫原性,并且由构象稳定的 CDV H 蛋白组装的纳米颗粒可以作为一种新型的犬瘟热疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d26e/8607554/60c8f937f99a/12985_2021_1702_Fig1_HTML.jpg

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