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重组疫苗的制备。

Preparation of recombinant vaccines.

作者信息

Soler Eric, Houdebine Louis-Marie

机构信息

Cell Biology Department, Erasmus MC, dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands.

出版信息

Biotechnol Annu Rev. 2007;13:65-94. doi: 10.1016/S1387-2656(07)13004-0.

Abstract

Vaccination is one of the most efficient ways to eradicate some infectious diseases in humans and animals. The material traditionally used as vaccines is attenuated or inactivated pathogens. This approach is sometimes limited by the fact that the material for vaccination is not efficient, not available, or generating deleterious side effects. A possible theoretical alternative is the use of recombinant proteins from the pathogens. This implies that the proteins having the capacity to vaccinate have been identified and that they can be produced in sufficient quantity at a low cost. Genetically modified organisms harboring pathogen genes can fulfil these conditions. Microorganisms, animal cells as well as transgenic plants and animals can be the source of recombinant vaccines. Each of these systems that are all getting improved has advantages and limits. Adjuvants must generally be added to the recombinant proteins to enhance their vaccinating capacity. This implies that the proteins used to vaccinate have been purified to avoid any immunization against the contaminants. The efficiency of a recombinant vaccine is poorly predictable. Multiple proteins and various modes of administration must therefore be empirically evaluated on a case-by-case basis. The structure of the recombinant proteins, the composition of the adjuvants and the mode of administration of the vaccines have a strong and not fully predictable impact on the immune response as well as the protection level against pathogens. Recombinant proteins can theoretically also be used as carriers for epitopes from other pathogens. The increasing knowledge of pathogen genomes and the availability of efficient systems to prepare large amounts of recombinant proteins greatly facilitate the potential use of recombinant proteins as vaccines. The present review is a critical analysis of the state of the art in this field.

摘要

疫苗接种是根除人类和动物某些传染病最有效的方法之一。传统上用作疫苗的材料是减毒或灭活的病原体。这种方法有时受到以下事实的限制:疫苗接种材料效率不高、无法获得或会产生有害副作用。一种可能的理论替代方法是使用病原体的重组蛋白。这意味着已经鉴定出具有疫苗接种能力的蛋白质,并且它们可以低成本大量生产。携带病原体基因的转基因生物可以满足这些条件。微生物、动物细胞以及转基因植物和动物都可以成为重组疫苗的来源。所有这些不断改进的系统都有优点和局限性。通常必须向重组蛋白中添加佐剂以增强其疫苗接种能力。这意味着用于疫苗接种的蛋白质已经过纯化,以避免针对污染物的任何免疫反应。重组疫苗的效率很难预测。因此,必须根据具体情况凭经验评估多种蛋白质和各种给药方式。重组蛋白的结构、佐剂的组成以及疫苗的给药方式对免疫反应以及针对病原体的保护水平具有强烈且不完全可预测的影响。理论上,重组蛋白也可以用作其他病原体表位的载体。对病原体基因组的了解不断增加以及制备大量重组蛋白的高效系统的可用性极大地促进了重组蛋白作为疫苗的潜在应用。本综述是对该领域现有技术水平的批判性分析。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b7c5/7106376/a8ff7fb15d78/gr1.jpg

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