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评价抗传染性胰脏坏死病毒(IPNV)不成熟病毒颗粒的免疫反应:一种开发减毒疫苗的新模型。

Evaluation of the immune response against immature viral particles of infectious pancreatic necrosis virus (IPNV): a new model to develop an attenuated vaccine.

机构信息

Laboratorio de Virología, Centro de Biotecnología Acuícola, Facultad de Química y Biología, Universidad de Santiago de Chile, 9170022 Santiago, Chile.

出版信息

Vaccine. 2012 Jul 20;30(34):5110-7. doi: 10.1016/j.vaccine.2012.05.062. Epub 2012 Jun 9.

Abstract

Infectious pancreatic necrosis virus (IPNV) is a worldwide problem affecting both freshwater and seawater fish. Vaccines developed against IPNV are not as efficient in the field as they are in tests. Moreover, research in the development of vaccines against IPNV has often shown that vaccines can stimulate the immune response of fish antibodies but do not protect efficiently against IPNV. In fact, sometimes dead infected fish show high antibody titers against IPNV. This suggests that the magnitude of total antibodies stimulated by the vaccine is not necessarily related to the level of protection against IPN, suggesting that a new method is needed to evaluate vaccine stimulation of the immune system. We propose in vitro evaluation of the non-specific cytotoxic cells (NCC) of the innate immune response, in addition to humoral specific response. Moreover, it is necessary to develop innovative methods to improve fish vaccines. In this work, IPNV replicative intermediaries (provirus) were used to inject rainbow trout fry, which is the most vulnerable state to IPNV. To evaluate the immune response triggered by this vaccine, NCC and total and neutralizing antibodies against IPNV and the provirus were determined. Results indicated that NCC activity in rainbow trout fry is triggered by IPNV infection. Both IPNV and the provirus stimulate humoral and NCC immune response in rainbow trout fry. Although the total antibodies triggered by the provirus were half of that triggered by IPNV infection, the number of neutralizing antibodies was similar in the two treatments. This suggests that the ratio of neutralizing antibodies is higher among the antibodies stimulated by provirons than among those stimulated by IPNV infection. Thus, immature provirus is sufficient to activate immune response and is a good candidate as an attenuated vaccine in rainbow trout fry. In addition, neutralizing antibodies, together with non-specific cytotoxic activity, are a more suitable strategy to evaluate new vaccines than humoral immune response alone.

摘要

传染性胰脏坏死病毒 (IPNV) 是一种影响淡水和海水鱼类的世界性问题。针对 IPNV 开发的疫苗在实际应用中的效果不如实验室测试中那么有效。此外,针对 IPNV 疫苗的研究经常表明,疫苗可以刺激鱼类抗体的免疫反应,但不能有效地保护鱼类免受 IPNV 的侵害。事实上,有时死亡感染的鱼类对 IPNV 表现出高抗体滴度。这表明疫苗刺激产生的总抗体的大小不一定与对 IPN 的保护水平相关,这表明需要一种新的方法来评估疫苗对免疫系统的刺激。我们建议除了体液特异性反应外,还可以在体外评估先天免疫反应的非特异性细胞毒性细胞 (NCC)。此外,有必要开发创新方法来改进鱼类疫苗。在这项工作中,我们使用 IPNV 复制中间体(前病毒)来注射彩虹鳟鱼苗,这是最容易感染 IPNV 的状态。为了评估这种疫苗引发的免疫反应,我们测定了 NCC 以及针对 IPNV 和前病毒的总抗体和中和抗体。结果表明,IPNV 感染会触发彩虹鳟鱼苗的 NCC 活性。IPNV 和前病毒都能刺激彩虹鳟鱼苗的体液和 NCC 免疫反应。尽管前病毒触发的总抗体是 IPNV 感染触发的一半,但两种处理方式产生的中和抗体数量相似。这表明前病毒刺激的抗体中中和抗体的比例高于 IPNV 感染刺激的抗体。因此,未成熟的前病毒足以激活免疫反应,是彩虹鳟鱼苗中减毒疫苗的良好候选物。此外,与单独的体液免疫反应相比,中和抗体与非特异性细胞毒性活性一起是评估新疫苗的更合适策略。

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