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虹鳟鱼接种疫苗并感染鲑鱼α病毒(SAV)后的细胞免疫反应

Cellular Immune Responses in Rainbow Trout () Following Vaccination and Challenge Against Salmonid Alphavirus (SAV).

作者信息

Veenstra Kimberly A, Hodneland Kjartan, Fischer Susanne, Takehana Kota, Belmonte Rodrigo, Fischer Uwe

机构信息

Friedrich-Loeffler-Institut (FLI), Federal Research Institute for Animal Health, Institute of Infectology, Südufer 10, 17493 Greifswald-Insel Riems, Germany.

MSD Animal Health Innovation, Thormøhlens Gate 55, 5006 Bergen, Norway.

出版信息

Vaccines (Basel). 2020 Dec 2;8(4):725. doi: 10.3390/vaccines8040725.

Abstract

Viral disease outbreaks remain a significant limiting factor for aquaculture. The majority of licensed vaccines used in the industry are administered as oil-adjuvanted formulations carrying inactivated whole pathogens. Cell-mediated immune responses, in particular those based on virus-specific cytotoxic T-cells (CTLs) to conventional inactivated oil-based vaccines, are largely unexplored. As vaccines cannot be optimized against viral pathogens if knowledge of host cellular immune mechanisms remains unknown, in this study we examined fundamental cell-mediated immune responses after vaccination of rainbow trout with an oil-adjuvanted inactivated vaccine against salmonid alphavirus (SAV) and after infection with SAV. A unique model system was developed to examine MHC class I restricted CTL responses in a clonal line of rainbow trout. The levels of cell-mediated cytotoxicity were compared to pathology, virus load, specific antibody response, changes in immune cell populations, and mRNA expression. Our results hint that different protective mechanisms are being triggered by infection compared to vaccination. While vaccination itself did not cause a strong cytotoxic or humoral response, subsequent challenge of vaccinated fish resulted in significantly stronger and faster specific cytotoxicity, alongside reduced viral titers and pathology. Hence, testing a vaccine on the capacity to induce cell-mediated cytotoxicity will still require a challenge test. Examination of cellular markers additionally indicates that the initial innate response induced by the vaccine could play an important role in steering adaptive mechanisms.

摘要

病毒性疾病爆发仍然是水产养殖的一个重要限制因素。该行业中使用的大多数许可疫苗都是以携带灭活全病原体的油佐剂制剂形式给药的。细胞介导的免疫反应,特别是那些基于针对传统灭活油基疫苗的病毒特异性细胞毒性T细胞(CTL)的反应,在很大程度上尚未得到探索。由于如果宿主细胞免疫机制的知识仍然未知,疫苗就无法针对病毒病原体进行优化,因此在本研究中,我们检测了虹鳟鱼接种抗鲑鱼α病毒(SAV)的油佐剂灭活疫苗后以及感染SAV后的基本细胞介导免疫反应。我们开发了一个独特的模型系统来检测虹鳟鱼克隆系中MHC I类限制性CTL反应。将细胞介导的细胞毒性水平与病理学、病毒载量、特异性抗体反应、免疫细胞群体变化和mRNA表达进行了比较。我们的结果表明,与接种疫苗相比,感染引发了不同的保护机制。虽然接种疫苗本身并未引起强烈的细胞毒性或体液反应,但对接种疫苗的鱼进行后续攻毒会导致明显更强、更快的特异性细胞毒性,同时病毒滴度和病理学表现降低。因此,测试疫苗诱导细胞介导细胞毒性的能力仍需要进行攻毒试验。对细胞标志物的检测还表明,疫苗诱导的初始先天反应可能在引导适应性机制方面发挥重要作用。

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