Department of Biological Systems Engineering, Virginia Tech, Blacksburg, VA, United States.
Locus Biosciences, Morrisville, NC, United States.
Front Immunol. 2020 Feb 24;11:283. doi: 10.3389/fimmu.2020.00283. eCollection 2020.
Today, vaccinologists have come to understand that the hallmark of any protective immune response is the antigen. However, it is not the whole antigen that dictates the immune response, but rather the various parts comprising the whole that are capable of influencing immunogenicity. Protein-based antigens hold particular importance within this structural approach to understanding immunity because, though different molecules can serve as antigens, only proteins are capable of inducing both cellular and humoral immunity. This fact, coupled with the versatility and customizability of proteins when considering vaccine design applications, makes protein-based vaccines (PBVs) one of today's most promising technologies for artificially inducing immunity. In this review, we follow the development of PBV technologies through time and discuss the antigen-specific receptors that are most critical to any immune response: pattern recognition receptors, B cell receptors, and T cell receptors. Knowledge of these receptors and their ligands has become exceptionally valuable in the field of vaccinology, where today it is possible to make drastic modifications to PBV structure, from primary to quaternary, in order to promote recognition of target epitopes, potentiate vaccine immunogenicity, and prevent antigen-associated complications. Additionally, these modifications have made it possible to control immune responses by modulating stability and targeting PBV to key immune cells. Consequently, careful consideration should be given to protein structure when designing PBVs in the future in order to potentiate PBV efficacy.
如今，疫苗学家已经认识到，任何保护性免疫反应的标志都是抗原。然而，决定免疫反应的不是整个抗原，而是构成整体的各种部分，它们能够影响免疫原性。在理解免疫的这种结构方法中，基于蛋白质的抗原具有特殊的重要性，因为尽管不同的分子可以作为抗原，但只有蛋白质能够诱导细胞和体液免疫。这一事实，加上在考虑疫苗设计应用时蛋白质的多功能性和可定制性，使得基于蛋白质的疫苗 (PBV) 成为当今最有前途的人工诱导免疫技术之一。在这篇综述中，我们跟踪 PBV 技术的发展历程，并讨论了对任何免疫反应最重要的抗原特异性受体：模式识别受体、B 细胞受体和 T 细胞受体。这些受体及其配体的知识在疫苗学领域变得非常有价值，在该领域，可以对 PBV 结构进行从一级到四级的剧烈修饰，以促进对靶表位的识别、增强疫苗免疫原性和防止抗原相关并发症。此外，这些修饰还使得通过调节稳定性和将 PBV 靶向关键免疫细胞来控制免疫反应成为可能。因此，在未来设计 PBV 时，应该仔细考虑蛋白质结构，以增强 PBV 的效力。
