Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, NY 14853, USA.
Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
Biotechnol Adv. 2023 Nov;68:108234. doi: 10.1016/j.biotechadv.2023.108234. Epub 2023 Aug 7.
Vaccines remain one of the most important pillars in preventative medicine, providing protection against a wide array of diseases by inducing humoral and/or cellular immunity. Of the many possible candidate antigens for subunit vaccine development, carbohydrates are particularly appealing because of their ubiquitous presence on the surface of all living cells, viruses, and parasites as well as their known interactions with both innate and adaptive immune cells. Indeed, several licensed vaccines leverage bacterial cell-surface carbohydrates as antigens for inducing antigen-specific plasma cells secreting protective antibodies and the development of memory T and B cells. Carbohydrates have also garnered attention in other aspects of vaccine development, for example, as adjuvants that enhance the immune response by either activating innate immune responses or targeting specific immune cells. Additionally, carbohydrates can function as immunomodulators that dampen undesired humoral immune responses to entire protein antigens or specific, conserved regions on antigenic proteins. In this review, we highlight how the interplay between carbohydrates and the adaptive and innate arms of the immune response is guiding the development of glycans as vaccine components that act as antigens, adjuvants, and immunomodulators. We also discuss how advances in the field of synthetic glycobiology are enabling the design, engineering, and production of this new generation of carbohydrate-containing vaccine formulations with the potential to prevent infectious diseases, malignancies, and complex immune disorders.
疫苗仍然是预防医学的重要支柱之一，通过诱导体液和/或细胞免疫来提供针对多种疾病的保护。在众多可能的亚单位疫苗候选抗原中，碳水化合物因其广泛存在于所有活细胞、病毒和寄生虫的表面以及它们与先天和适应性免疫细胞的已知相互作用而特别吸引人。事实上，几种已获得许可的疫苗利用细菌细胞表面碳水化合物作为抗原，诱导产生特异性浆细胞，从而分泌保护性抗体，并产生记忆 T 和 B 细胞。碳水化合物在疫苗开发的其他方面也引起了关注，例如作为佐剂，通过激活先天免疫反应或靶向特定免疫细胞来增强免疫反应。此外，碳水化合物可以作为免疫调节剂，抑制对整个蛋白质抗原或抗原蛋白上特定保守区域的不希望的体液免疫反应。在这篇综述中，我们强调了碳水化合物与适应性和先天免疫反应之间的相互作用如何指导糖作为疫苗成分的开发，这些成分可作为抗原、佐剂和免疫调节剂。我们还讨论了合成糖生物学领域的进展如何使新一代含有碳水化合物的疫苗配方的设计、工程和生产成为可能，这些疫苗有可能预防传染病、恶性肿瘤和复杂的免疫性疾病。
