Synthetic peptide immunogens as vaccines.
Synthetic peptide immunogens as vaccines.
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作为疫苗的合成肽免疫原。
DOI：
--
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发表时间：
1983
影响因子：
10.5
通讯作者：
R. Lerner
中科院分区：
文献类型：
--
作者：
T. Shinnick;J. Sutcliffe;N. Green;R. Lerner
合成肽免疫原已被证明可以诱导抗体，这些抗体可以与含有该肽的全长蛋白质发生反应。这种抗体是针对研究人员预先选择的蛋白质的特定区域，因此具有预定的特异性。在基础研究中，这些抗体用于识别开放阅读框架的蛋白质产物，将基因产物定位于特定细胞或亚细胞细胞器，识别蛋白质产物的酶功能，通过蛋白质成熟过程跟踪产物特定区域的命运，分析DNA重排和RNA剪接后外显子的表达，以及通过免疫亲和层析技术纯化蛋白质。在医学上，这种抗体可以为被动疫苗接种、抗毒素治疗和肿瘤的靶向免疫治疗提供试剂。这些多肽本身可以用作合成疫苗。合成肽免疫原在医学上的近期前景是明确的--在实验室展示的前景必须减少到在医院安全应用。要做到这一点，有两个障碍，一是选择最好的多肽，二是选择合适的佐剂。目前，一种强力方法被用来寻找产生所需抗体的最佳多肽。这显然是一个问题，因为只有在人类身上才能检测到病原体。通过将对病原体抗原性的研究与对改变其免疫原性的自然产生的变异的分析结合起来，可能会使肽的选择变得更容易。此外，由于实验室中使用的佐剂和载体通常过于苛刻，无法在人类和动物中广泛使用，因此需要做很多工作来寻找合适的佐剂和载体。尽管如此，既然合成肽疫苗的主要概念障碍已经清除(即没有必要精确复制构象)，解决剩余问题应该相对简单。
Synthetic peptide immunogens have been shown to elicit antibodies that can react with full-length proteins containing that peptide. Such antibodies are directed against a specific region of the protein chosen in advance by the investigator and so have a predetermined specificity. In basic research, these antibodies are useful in identifying the protein product of an open reading frame, localizing the gene product to particular cells or subcellular organelles, identifying the enzymatic function of a protein product, following the fate of particular regions of a product through protein maturation processes, analyzing the expression of exons following DNA rearrangements and RNA splicing, and purifying the protein by immunoaffinity chromatography techniques. In medicine, such antibodies may provide reagents for passive vaccination, antitoxin therapy, and targeted immunotherapy of neoplasia. The peptides themselves may be used as synthetic vaccines. The immediate future of the synthetic peptide immunogen in medicine is clear--the promise demonstrated in the laboratory must be reduced to safe application in the hospital. Two barriers to this are the selection of precisely the best peptide and the selection of the proper adjuvant. Currently, a brute force approach is utilized to find the best peptide for eliciting the desired antibodies. This is clearly a problem when the pathogenic organism is assayable only in man. Possibly, by combining studies on the antigenicity of the pathogenic organism with an analysis of naturally occurring variants that alter its immunogenicity, peptide selection will be made easier. Also, since the adjuvants and carriers used in the laboratory are in general too harsh for widespread use in humans and animals, much work needs to be done to find suitable adjuvants and carriers. Nonetheless, now that the major conceptual hurdle to synthetic peptide vaccines has been cleared (that is, it is not necessary to reproduce conformation exactly), it should be relatively straightforward to solve the remaining problems.