New Routes and Opportunities for Modular Construction of Particulate Vaccines: Stick, Click, and Glue.

New Routes and Opportunities for Modular Construction of Particulate Vaccines: Stick, Click, and Glue.
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DOI:
10.3389/fimmu.2018.01432
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发表时间:
2018
影响因子:
7.3
通讯作者:
Howarth M
Howarth M
中科院分区:
医学2区
文献类型:
--
作者:
Brune KD;Howarth M

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基于病毒样颗粒(VLP)的疫苗可以诱导有效的B细胞应答。一些基于非嵌合VLP的疫苗是非常成功的许可产品(例如,作为B型肝炎病毒疫苗的B型肝炎表面抗原VLP)。嵌合VLP被设计为通过用不同的抗原装饰VLP来利用VLP框架。尽管经过几十年的努力,很少有许可的嵌合VLP疫苗。产生嵌合VLP的经典方法是基因融合或化学缀合,使用从VLP上的赖氨酸到抗原上的半胱氨酸的交联剂。我们描述的原则,使这些经典的方法具有挑战性,特别是复杂的,全长抗原承载多个翻译后修饰。然后,我们回顾了最近的进展,结合蛋白质为基础的无包膜VLP或纳米粒子的方法,以克服这些挑战。这包括使用强非共价组装方法(粘),用于生物正交化学的非天然氨基酸(点击),以及SpyTag/SpyCatcher(胶)的自发异肽键形成。现有的应用程序,这些方法的概述,我们认真考虑的关键实际问题,特别是洞察标签/捕手插件和显示装饰。最后,我们强调了模块化颗粒装饰的潜力,以加速疫苗的产生,并为人类和兽医领域的大流行威胁做好准备。
Vaccines based on virus-like particles (VLPs) can induce potent B cell responses. Some non-chimeric VLP-based vaccines are highly successful licensed products (e.g., hepatitis B surface antigen VLPs as a hepatitis B virus vaccine). Chimeric VLPs are designed to take advantage of the VLP framework by decorating the VLP with a different antigen. Despite decades of effort, there have been few licensed chimeric VLP vaccines. Classic approaches to create chimeric VLPs are either genetic fusion or chemical conjugation, using cross-linkers from lysine on the VLP to cysteine on the antigen. We describe the principles that make these classic approaches challenging, in particular for complex, full-length antigens bearing multiple post-translational modifications. We then review recent advances in conjugation approaches for protein-based non-enveloped VLPs or nanoparticles, to overcome such challenges. This includes the use of strong non-covalent assembly methods (stick), unnatural amino acids for bio-orthogonal chemistry (click), and spontaneous isopeptide bond formation by SpyTag/SpyCatcher (glue). Existing applications of these methods are outlined and we critically consider the key practical issues, with particular insight on Tag/Catcher plug-and-display decoration. Finally, we highlight the potential for modular particle decoration to accelerate vaccine generation and prepare for pandemic threats in human and veterinary realms.
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