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树突状细胞靶向重组乳杆菌诱导树突状细胞活化并引发针对禽 H9N2 流感病毒 G57 基因型的特异性免疫应答。

Dendritic cell-targeted recombinantLactobacilli induce DC activation and elicit specific immune responses against G57 genotype of avian H9N2 influenza virus infection.

机构信息

Engineering Research Center of Jilin Province for Animals Probiotics, College of Animal Science and Technology, Jilin Agricultural University, Changchun, China.

Laboratory of Infectious Diseases, College of Veterinary Medicine, Jilin University, Changchun, China; Key Laboratory of Zoonosis Research, Ministry of Education, Jilin University, Changchun, China.

出版信息

Vet Microbiol. 2018 Sep;223:9-20. doi: 10.1016/j.vetmic.2018.07.009. Epub 2018 Jul 17.

Abstract

H9N2 avian influenza viruses are of significance in poultry and public health for the past two decades. Vaccination plays an important role in preventing the infection in domestic poultry. Current H9N2 vaccines have not yet offered ideal protection and eliminated shedding of G57 genotype viruses responsible for H9N2 outbreaks during 2010-2013. Targeted vaccination is a promising strategy to improve vaccine effectiveness. Such a vaccine strategy can be achieved if it is targeted to dendritic cells (DCs) that directly elicit mucosal and adaptive immune responses against microbe challenge. For this purpose, we develop a DC-targeted mucosal vaccine for the oral delivery of the HA protein fused to a DCpep by using Lactobacillus plantarum as an antigen delivery system against G57 virus infection. It showed that Lactobacillus plantarum expressing HA-DCpep confers efficient protection against G57 H9N2 infection, due to have the potential to activate DCs by the TLR-induced NF-κB pathway, to promote DC migration by the CCR7-CCL19/CCL21 axis, thereby enhancing the presentation of immunogen to T and B lymphocytes, resulting in skewing T cells polarization towards Th1, Th2 and Treg cells and evoking more efficient mucosal and adaptive immunity responses. The presented oral mucosal vaccine strategy illustrates the feasibility and efficacy of antigen targeting to DCs through genetic fusion of vaccines to DC-targeting peptides and aids in the design and selection of indications that could be used with this oral vaccine platform against influenza.

摘要

在过去的二十年中,H9N2 禽流感病毒对家禽和公共卫生具有重要意义。疫苗接种在预防家禽感染方面发挥着重要作用。目前的 H9N2 疫苗尚未提供理想的保护,也未能消除导致 2010-2013 年 H9N2 疫情爆发的 G57 基因型病毒的脱落。靶向疫苗接种是提高疫苗效果的一种有前途的策略。如果这种疫苗策略针对树突状细胞 (DC),可以直接引发针对微生物挑战的粘膜和适应性免疫反应,那么就可以实现这种疫苗策略。为此,我们开发了一种针对 DC 的粘膜疫苗,用于通过乳杆菌属植物作为抗原传递系统口服递送融合有 DCpep 的 HA 蛋白,以对抗 G57 病毒感染。结果表明,由于能够通过 TLR 诱导的 NF-κB 途径激活 DC,通过 CCR7-CCL19/CCL21 轴促进 DC 迁移,从而增强免疫原向 T 和 B 淋巴细胞的呈递,导致 T 细胞向 Th1、Th2 和 Treg 细胞的极化偏向,引发更有效的粘膜和适应性免疫反应,因此,表达 HA-DCpep 的乳杆菌属植物能够有效地预防 G57 H9N2 感染。所提出的口服粘膜疫苗策略说明了通过将疫苗与 DC 靶向肽进行基因融合将抗原靶向 DC 的可行性和有效性,并有助于针对流感设计和选择可用于这种口服疫苗平台的适应症。

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