Epitope mapping: the first step in developing epitope-based vaccines.
Epitope mapping: the first step in developing epitope-based vaccines.
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DOI：
10.2165/00063030-200721030-00002
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Weiss Y
中科院分区：
文献类型：
--
作者：
Gershoni JM;Roitburd-Berman A;Siman-Tov DD;Tarnovitski Freund N;Weiss Y
抗体是预防传染病的有效防线。高效中和抗体可以在病毒附着到靶细胞之前拦截病毒，从而将其消灭。这种能力基于抗体对抗原表位的特异性识别，抗原表位是抗体结合的抗原位点。因此，了解抗体/表位相互作用为预防性疫苗的合理设计提供了基础。假设用对应于有效中和抗体的精确表位免疫接种将在疫苗接种者中引发类似有效抗体的产生。这样的疫苗将是“基于B细胞表位的疫苗”，其实施需要从所需抗体回溯到其相应表位的能力。在这篇文章中，我们讨论了一系列的方法，使表位发现的基础上的特定抗体。这种反向免疫学方法是基于表位的疫苗的合理设计的第一步。毫无疑问，表位定义的金标准是抗原：抗体复合物晶体的X射线分析。该方法提供了表位的原子分辨率;然而，它不容易适用于许多抗原和抗体，并且需要非常高的复杂度和专业知识。大多数其他方法依赖于监测抗体与抗原片段或突变变体的结合的能力。在抗原的诱变中，由于氨基酸残基的点修饰导致的结合丧失通常被认为是表位组分的指示。此外，用于表位作图的计算组合方法也是有用的。这些方法依赖于目标抗体从组合噬菌体展示肽文库中亲和分离特异性短肽的能力。然后将肽视为定义对应于用于筛选肽文库的抗体的表位的先导。对于表位作图，已经开发了计算算法，例如Mapitope，最近发现其在作图构象不连续表位中是有效的。表位作图的各种方法的利弊也进行了讨论。
Antibodies are an effective line of defense in preventing infectious diseases. Highly potent neutralizing antibodies can intercept a virus before it attaches to its target cell and, thus, inactivate it. This ability is based on the antibodies’ specific recognition of epitopes, the sites of the antigen to which antibodies bind. Thus, understanding the antibody/epitope interaction provides a basis for the rational design of preventive vaccines. It is assumed that immunization with the precise epitope, corresponding to an effective neutralizing antibody, would elicit the generation of similarly potent antibodies in the vaccinee. Such a vaccine would be a ‘B-cell epitope-based vaccine’, the implementation of which requires the ability to backtrack from a desired antibody to its corresponding epitope. In this article we discuss a range of methods that enable epitope discovery based on a specific antibody. Such a reversed immunological approach is the first step in the rational design of an epitope-based vaccine. Undoubtedly, the gold standard for epitope definition is x-ray analyses of crystals of antigen: antibody complexes. This method provides atomic resolution of the epitope; however, it is not readily applicable to many antigens and antibodies, and requires a very high degree of sophistication and expertise. Most other methods rely on the ability to monitor the binding of the antibody to antigen fragments or mutated variations. In mutagenesis of the antigen, loss of binding due to point modification of an amino acid residue is often considered an indication of an epitope component. In addition, computational combinatorial methods for epitope mapping are also useful. These methods rely on the ability of the antibody of interest to affinity isolate specific short peptides from combinatorial phage display peptide libraries. The peptides are then regarded as leads for the definition of the epitope corresponding to the antibody used to screen the peptide library. For epitope mapping, computational algorithms have been developed, such as Mapitope, which has recently been found to be effective in mapping conformational discontinuous epitopes. The pros and cons of various approaches towards epitope mapping are also discussed.
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DOI：
10.1073/pnas.84.23.8583
发表时间：
1987-12-01
影响因子：
11.1
作者：
ARTHUR, LO;PYLE, SW;FISCHINGER, PJ
通讯作者：
FISCHINGER, PJ
影响因子：
2.4
作者：
Füst, G
通讯作者：
Füst, G
DOI：
10.1002/prot.340190303
发表时间：
1994-07-01
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
DINOLA, A;ROCCATANO, D;BERENDSEN, HJC
通讯作者：
BERENDSEN, HJC
影响因子：
2.7
作者：
Fleming, TJ;Sachdeva, M;Sexton, DJ
通讯作者：
Sexton, DJ
影响因子：
4.8
作者：
Burns, EL;Nicholas, RA;Price, EM
通讯作者：
Price, EM