Brune Karl D, Howarth Mark
Department of Bioengineering, Imperial College London, London, United Kingdom.
Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
Front Immunol. 2018 Jun 26;9:1432. doi: 10.3389/fimmu.2018.01432. eCollection 2018.
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.
基于病毒样颗粒（VLP）的疫苗可诱导强烈的B细胞反应。一些基于非嵌合VLP的疫苗是非常成功的获批产品（例如，乙肝表面抗原VLP作为乙肝病毒疫苗）。嵌合VLP旨在通过用不同抗原修饰VLP来利用VLP框架。尽管经过了数十年的努力，但获批的嵌合VLP疫苗却很少。创建嵌合VLP的经典方法是基因融合或化学偶联，使用从VLP上的赖氨酸到抗原上的半胱氨酸的交联剂。我们描述了使这些经典方法具有挑战性的原理，特别是对于带有多种翻译后修饰的复杂全长抗原。然后，我们回顾了基于蛋白质的非包膜VLP或纳米颗粒偶联方法的最新进展，以克服此类挑战。这包括使用强大的非共价组装方法（粘贴）、用于生物正交化学的非天然氨基酸（点击）以及通过SpyTag/SpyCatcher形成自发异肽键（胶水）。概述了这些方法的现有应用，我们批判性地考虑了关键的实际问题，特别是对标签/捕获器即插即用修饰的见解。最后，我们强调了模块化颗粒修饰在加速疫苗研发以及为人类和兽医领域的大流行威胁做准备方面的潜力。
