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用病毒抗原进行免疫接种:传染性胰腺坏死病

Immunization with viral antigens: infectious pancreatic necrosis.

作者信息

Christie K E

机构信息

Intervet Norbio AS, Bergen, Norway.

出版信息

Dev Biol Stand. 1997;90:191-9.

PMID:9270848
Abstract

Clinical IPN has traditionally been observed in brook trout (Salvelinus fontinalis) and rainbow trout (Oncorhynchus mykiss). However, during the past 10 years outbreaks of IPN have been reported frequently in farmed Atlantic salmon (Salmo salar L.) in Norway. Acute IPN with high mortality is observed in fry at start feeding and in smolt in the first six months after transfer to seawater. Today IPN is the most important infectious disease in Norway in farmed fish, giving economic losses of about 60 million USD yearly. A prophylactic strategy against this disease is strongly needed. Different strategies for developing IPN vaccines have been tested since the virus was first isolated in 1960. Vaccination with live virus has not been successful and is probably not an acceptable strategy for environmental risk reasons. Vaccination with inactivated virus has been tested in rainbow trout given by the oral route, by immersion and injection. Protection against challenge was obtained only by injection. IPN vaccines based on inactivated virus may be effective but are expensive. A subunit vaccine produced by fermentation is a more realistic strategy for fish vaccine production if the actual protective epitopes can be identified. Protective IPNV epitopes may include both B- and T-cell epitopes, but only B-cell epitopes have been examined so far. Epitope mapping with neutralising monoclonal antibodies indicates that the internal variable region of VP2 (aa 200-350) folds into an immunodominant structure including both serotype specific and conserved neutralisation epitopes that can renaturate spontaneously from E. coli-expressed recombinant VP2 (rVP2). Analysis with an IPNV group-A specific neutralising monoclonal antibody indicates that immunisation with recombinant protein containing the segment (aa 86-210) might induce protection against all IPNV serotypes. Subunit vaccines based on E. coli-expressed IPNV proteins have been tested in rainbow trout and Atlantic salmon. Vaccination by immersion in rainbow trout fry with bacterial lysate from E. coli expressing the IPNV Sp strain gene segment A induced protection against challenge with the IPNV Buhl strain. By injection of Atlantic salmon parr with partly purified E. coli-expressed rVP2 (N1 strain), increased resistance against IPN infection was demonstrated by challenge. In field trials it is shown that vaccination of pre-smolt with rVP2 included in a commercial oil/glucan adjuvanted multivalent bacterial vaccine gives protection against IPN in natural outbreaks, compared to fish vaccinated with the same vaccine without the IPNV component.

摘要

传统上,临床传染性胰脏坏死病(IPN)多见于溪红点鲑(Salvelinus fontinalis)和虹鳟(Oncorhynchus mykiss)。然而,在过去10年里,挪威养殖的大西洋鲑(Salmo salar L.)频繁暴发IPN疫情。开始摄食的鱼苗以及转入海水后的头六个月的幼鲑中会出现高死亡率的急性IPN。如今,IPN是挪威养殖鱼类中最重要的传染病,每年造成约6000万美元的经济损失。因此,迫切需要针对这种疾病的预防策略。自1960年首次分离出该病毒以来,人们已经测试了多种研发IPN疫苗的策略。用活病毒进行疫苗接种未获成功,出于环境风险考虑,这可能不是一种可接受的策略。用灭活病毒进行疫苗接种已在虹鳟中通过口服、浸泡和注射等途径进行了测试。仅通过注射才能获得针对攻毒的保护。基于灭活病毒的IPN疫苗可能有效,但成本高昂。如果能够确定实际的保护性表位,那么通过发酵生产的亚单位疫苗对于鱼类疫苗生产来说是一种更现实的策略。保护性IPN病毒(IPNV)表位可能包括B细胞和T细胞表位,但迄今为止仅对B细胞表位进行了研究。用中和性单克隆抗体进行的表位图谱分析表明,VP2的内部可变区(氨基酸200 - 350)折叠成一种免疫显性结构,其中包括血清型特异性和保守的中和表位,这些表位可以从大肠杆菌表达的重组VP2(rVP2)中自发复性。用IPNV A组特异性中和单克隆抗体进行分析表明,用含有该片段(氨基酸86 - 210)的重组蛋白进行免疫接种可能诱导针对所有IPNV血清型的保护。基于大肠杆菌表达的IPNV蛋白的亚单位疫苗已在虹鳟和大西洋鲑中进行了测试。用表达IPNV Sp株基因片段A的大肠杆菌细菌裂解物浸泡虹鳟鱼苗可诱导其产生针对IPNV布尔株攻毒的保护。通过向大西洋鲑幼鱼注射部分纯化的大肠杆菌表达的rVP2(N1株),攻毒试验表明其对IPN感染的抵抗力增强。在田间试验中发现,与接种不含IPNV成分的相同疫苗的鱼相比,用商业油/葡聚糖佐剂多价细菌疫苗中包含的rVP2对即将转入海水养殖的鱼苗进行接种,可在自然暴发疫情时预防IPN。

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