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用核苷酸、脂质体或矿物油佐剂配制的注射疫苗在虹鳟鱼中诱导出不同的免疫原性差异。

Injection Vaccines Formulated with Nucleotide, Liposomal or Mineral Oil Adjuvants Induce Distinct Differences in Immunogenicity in Rainbow Trout.

作者信息

Villumsen Kasper Rømer, Kania Per Walter, Christensen Dennis, Koppang Erling Olaf, Bojesen Anders Miki

机构信息

Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, DK-1870 Frederiksberg, Denmark.

Adjuvant Research, Statens Serum Institut, DK-2300 Copenhagen S, Denmark.

出版信息

Vaccines (Basel). 2020 Feb 25;8(1):103. doi: 10.3390/vaccines8010103.

DOI:10.3390/vaccines8010103
PMID:32106599
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7157222/
Abstract

Protection facilitated by the widespread use of mineral oil adjuvanted injection vaccines in salmonid fish comes with adverse effects of varying severity. In this study, we characterized the immunological profiles of two alternative vaccine formulations, both with proven efficacy and an improved safety profile in rainbow trout. Experimental injection vaccines were prepared on an identical whole-cell bacterin platform and were formulated with CpG oligodeoxynucleotides, a liposomal (CAF01) or a benchmark mineral oil adjuvant, respectively. A naïve group, as well as bacterin and saline-injected groups were also included. Following administration, antigen-specific serum antibody titers, the tissue distribution of immune cell markers, and the expression of immune-relevant genes following the in vitro antigenic restimulation of anterior kidney leukocytes was investigated. Immunohistochemical staining suggested prolonged antigen presentation for the particulate formulations and increased mucosal presence of antigen-presenting cells in all immunized fish. Unlike the other immunized groups, the CAF01 group only displayed a transient elevation in specific antibody titers and immunohistochemical observations, and the transcription data suggest an increased role of cell-mediated immunity for this group. Finally, the transcription profile of the CpG formulation approached that of a T profile. When compared to the benchmark formulation, CAF01 and CpG adjuvants induce slight, but distinct differences in the resulting protective immune responses. This is important, as it allows a broader immunological approach for the future development of safer vaccines.

摘要

在鲑科鱼类中广泛使用矿物油佐剂注射疫苗带来的保护作用伴随着不同严重程度的不良反应。在本研究中,我们对两种替代疫苗制剂的免疫特征进行了表征,这两种制剂在虹鳟鱼中均已证明具有疗效且安全性有所改善。实验性注射疫苗是在相同的全细胞菌苗平台上制备的,分别用CpG寡脱氧核苷酸、脂质体(CAF01)或基准矿物油佐剂进行配制。还包括一个未免疫组以及注射菌苗和生理盐水的组。给药后,研究了抗原特异性血清抗体滴度、免疫细胞标志物的组织分布以及前肾白细胞体外抗原再刺激后免疫相关基因的表达。免疫组织化学染色表明,颗粒制剂的抗原呈递时间延长,且所有免疫鱼中抗原呈递细胞的黏膜存在增加。与其他免疫组不同,CAF01组仅显示特异性抗体滴度和免疫组织化学观察结果有短暂升高,转录数据表明该组细胞介导的免疫作用增强。最后,CpG制剂的转录谱接近T细胞谱。与基准制剂相比,CAF01和CpG佐剂在产生的保护性免疫反应中诱导出轻微但明显的差异。这很重要,因为它为未来开发更安全的疫苗提供了更广泛的免疫学方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9d2/7157222/b30a19cbbcfd/vaccines-08-00103-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9d2/7157222/c36b4e8e08c6/vaccines-08-00103-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9d2/7157222/e5ebe95a31bb/vaccines-08-00103-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9d2/7157222/b30a19cbbcfd/vaccines-08-00103-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9d2/7157222/c36b4e8e08c6/vaccines-08-00103-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9d2/7157222/e5ebe95a31bb/vaccines-08-00103-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c9d2/7157222/b30a19cbbcfd/vaccines-08-00103-g003.jpg

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本文引用的文献

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Sci Rep. 2017 Jul 19;7(1):5930. doi: 10.1038/s41598-017-06324-7.
2
Analysis of adipose tissue immune gene expression after vaccination of rainbow trout with adjuvanted bacterins reveals an association with side effects.用佐剂菌苗对虹鳟进行疫苗接种后,对脂肪组织免疫基因表达的分析揭示了其与副作用之间的关联。
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Int J Mol Sci. 2020 Jul 20;21(14):5122. doi: 10.3390/ijms21145122.
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Sci Rep. 2016 Jan 21;6:19570. doi: 10.1038/srep19570.
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Yersinia ruckeri lipopolysaccharide is necessary and sufficient for eliciting a protective immune response in rainbow trout (Oncorhynchus mykiss, Walbaum).鲁氏耶尔森菌脂多糖对于在虹鳟(Oncorhynchus mykiss, Walbaum)中引发保护性免疫反应是必要且充分的。
Fish Shellfish Immunol. 2016 Feb;49:420-6. doi: 10.1016/j.fsi.2015.12.037. Epub 2016 Jan 4.
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Global 3D imaging of Yersinia ruckeri bacterin uptake in rainbow trout fry.鲁氏耶尔森菌疫苗在虹鳟鱼苗中摄取情况的整体三维成像
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Controls for immunohistochemistry: the Histochemical Society's standards of practice for validation of immunohistochemical assays.免疫组织化学对照:组织化学学会免疫组织化学检测验证的实践标准。
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Transfer of serum and cells from Yersinia ruckeri vaccinated doubled-haploid hot creek rainbow trout into outcross F1 progeny elucidates mechanisms of vaccine-induced protection.血清和细胞从接种双单倍体虹鳟鱼弧菌疫苗转移到杂交 F1 后代中,阐明了疫苗诱导保护的机制。
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Long-lasting protection induced by bath vaccination against Aeromonas salmonicida subsp. salmonicida in rainbow trout.经浴水接种预防鲑鱼气单胞菌亚种鲑鱼对虹鳟鱼的持久保护。
Fish Shellfish Immunol. 2013 Nov;35(5):1649-53. doi: 10.1016/j.fsi.2013.09.013. Epub 2013 Sep 19.