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抗球虫病重组疫苗研发进展。综述与对下一个千年的展望。

Progress in recombinant vaccine development against coccidiosis. A review and prospects into the next millennium.

作者信息

Vermeulen A N

机构信息

Department of Parasitology, Intervet International BV, AA Boxmeer, The Netherlands.

出版信息

Int J Parasitol. 1998 Jul;28(7):1121-30. doi: 10.1016/s0020-7519(98)00080-0.

Abstract

The increasing problems encountered by the poultry industry, despite the extensive use of drugs, have emphasised the need for an immunological solution for the economic damage caused by the Eimeria parasite. Although immunity develops relatively fast following a natural infection, to induce protection by using parasite extracts or single antigens appears more difficult. Nevertheless, the development of a vaccine based on defined antigens seems the best solution in the long run. At the VIth International Coccidiosis Conference in 1993 the first promising results were reported from small-scale experiments using recombinant antigens. This review summarises the advances in this field of research from 1993 onwards. Although since then not many reports have been published about the effects of using recombinant. antigens as a vaccine against coccidiosis, a number of interesting new proteins which could be considered good targets for such a vaccine have been described and are referred to herein. Proteins involved in the process of invasion of the host cell by the extracellular parasite are regarded as key components in the developmental cycle of the parasite. These components possibly bind to receptors on the host cell. Interference with this process could be a target of the protective immune response. Progress has also been made in characterising the immune mechanisms activated by infection with the parasite. From experimental mouse models and from studies in chickens, a better insight has been obtained towards the involvement of CD4- and CD8-type T cells in, respectively, the inductor and the effector branch of the immune response, although not all questions have been answered. Several antigens have been selected using T-cell stimulation and cytokine assays and these are reviewed. In a third section, mostly unpublished results of our own experiments dealing with the use of live vectors to present defined antigens such as Ea1A and EaSC2, a parasite refractile body transhydrogenase and a lactate dehydrogenase, respectively, are summarised. Partial protection could be induced using Salmonella typhimurium as a carrier for these antigens, in that the oocyst output was reduced by up to 50% after challenge and weight gain could be improved by 5-10% over non-vaccinated challenged chickens, when tested in a floor-pen trial. Similar results were obtained when these antigens were presented by viral vectors such as Fowlpox virus or Herpes virus of turkey. These data seem to offer good prospects for the accomplishment of a safe and efficaceous vaccine based on recombinant DNA technology. These expectations are corroborated by recent breakthrough in transfection of related parasites such as Plasmodium and Toxoplasma gondii, and by the increasing amount of genomic information becoming available every day, the impact of which cannot even be estimated yet. These new technologies will allow us to solve the complex problems that we once created ourselves.

摘要

尽管广泛使用药物,家禽业面临的问题却日益增多,这凸显了针对艾美耳球虫寄生虫造成的经济损失寻求免疫解决方案的必要性。虽然自然感染后免疫力发展相对较快,但利用寄生虫提取物或单一抗原诱导保护似乎更困难。然而,从长远来看,开发基于特定抗原的疫苗似乎是最佳解决方案。在1993年第六届国际球虫病会议上,小规模的使用重组抗原的实验报告了首批有前景的结果。本综述总结了1993年以来该研究领域的进展。尽管自那时以来关于使用重组抗原作为抗球虫病疫苗效果的报道不多,但已描述了一些可能被视为这种疫苗良好靶点的有趣新蛋白,并在此提及。细胞外寄生虫侵入宿主细胞过程中涉及的蛋白质被视为寄生虫发育周期中的关键成分。这些成分可能与宿主细胞上的受体结合。干扰这一过程可能是保护性免疫反应的靶点。在表征由寄生虫感染激活的免疫机制方面也取得了进展。从小鼠实验模型和鸡的研究中,对CD4和CD8型T细胞分别在免疫反应的诱导和效应分支中的作用有了更好的了解,尽管并非所有问题都已得到解答。利用T细胞刺激和细胞因子检测筛选出了几种抗原,并在此进行综述。在第三部分,总结了我们自己实验的大多未发表结果,这些实验分别涉及使用活载体呈递特定抗原,如Ea1A和EaSC2、一种寄生虫折光体转氢酶和一种乳酸脱氢酶。在地面围栏试验中进行测试时,使用鼠伤寒沙门氏菌作为这些抗原的载体可诱导部分保护,即攻毒后卵囊产量降低多达50%,与未接种疫苗且受攻毒的鸡相比,体重增加可提高5% - 10%。当这些抗原由禽痘病毒或火鸡疱疹病毒等病毒载体呈递时,也获得了类似结果。这些数据似乎为基于重组DNA技术开发安全有效的疫苗提供了良好前景。近期在疟原虫和弓形虫等相关寄生虫转染方面的突破以及每天可获取的基因组信息数量不断增加,证实了这些期望,其影响甚至尚未能估量。这些新技术将使我们能够解决我们自己曾经制造的复杂问题。

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