The development of subunit vaccine platforms has been of considerable interest due to their good safety profile and ability to be adapted to new antigens, compared to other vaccine typess. Nevertheless, subunit vaccines often lack sufficient immunogenicity to fully protect against infectious diseases. A wide variety of subunit vaccines have been developed to enhance antigen immunogenicity by increasing antigen multivalency, as well as stability and delivery properties, via presentation of antigens on protein nanoparticles. Increasing multivalency can be an effective approach to provide a potent humoral immune response by more strongly engaging and clustering B cell receptors (BCRs) to induce activation, as well as increased uptake by antigen presenting cells and their subsequent T cell activation. Proper orientation of antigen on protein nanoparticles is also considered a crucial factor for enhanced BCR engagement and subsequent immune responses. Therefore, various strategies have been reported to decorate highly repetitive surfaces of protein nanoparticle scaffolds with multiple copies of antigens, arrange antigens in proper orientation, or combinations thereof. In this review, we describe different chemical bioconjugation methods, approaches for genetic fusion of recombinant antigens, biological affinity tags, and enzymatic conjugation methods to effectively present antigens on the surface of protein nanoparticle vaccine scaffolds.

中文翻译：

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开发多价蛋白质疫苗纳米粒子的化学和生物缀合策略

与其他疫苗类型相比，亚单位疫苗平台的开发由于其良好的安全性和适应新抗原的能力而引起了相当大的兴趣。然而，亚单位疫苗往往缺乏足够的免疫原性来充分预防传染病。已经开发出多种亚单位疫苗，通过在蛋白质纳米粒子上呈递抗原来增加抗原的多价性以及稳定性和递送特性，从而增强抗原的免疫原性。增加多价性可以是一种有效的方法，通过更强烈地接合和聚集 B 细胞受体 (BCR) 来诱导激活，以及增加抗原呈递细胞的摄取及其随后的 T 细胞激活，从而提供有效的体液免疫应答。蛋白质纳米颗粒上抗原的正确定向也被认为是增强 BCR 结合和随后免疫反应的关键因素。因此，已经报道了多种策略来用抗原的多个拷贝来装饰蛋白质纳米颗粒支架的高度重复的表面、以正确的方向排列抗原或其组合。在这篇综述中，我们描述了不同的化学生物缀合方法、重组抗原的基因融合方法、生物亲和标签和酶促缀合方法，以有效地将抗原呈现在蛋白质纳米颗粒疫苗支架的表面上。