Self-assembling protein nanoparticles in the design of vaccines.
Self-assembling protein nanoparticles in the design of vaccines.
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DOI：
10.1016/j.csbj.2015.11.001
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发表时间：
2016
影响因子：
6
通讯作者：
Bottomley MJ
中科院分区：
文献类型：
--
作者：
López-Sagaseta J;Malito E;Rappuoli R;Bottomley MJ
一百多年来，疫苗一直是减少传染病最有效的医疗干预措施之一，据估计每年可挽救全球数百万人的生命。然而，许多疾病仍无法通过疫苗接种来预防。这一巨大的未满足的医疗需求需要进一步研究和开发高效、安全的新型疫苗。与 19 世纪和 20 世纪初由灭活、灭活或减毒活病原体制成的疫苗相比，含有分离的、高度纯化的抗原蛋白亚基的现代疫苗更安全，但往往会诱导较低水平的保护性免疫。克服后者的一种策略是设计抗原纳米颗粒：多肽的组装体，以有序的阵列呈现亚基抗原的多个副本，具有明确的方向，可以潜在地模拟自然宿主-病原体表面相互作用的重复性、几何形状、大小和形状。这种纳米粒子提供了多个结合位点的集体强度（亲和力），并且可以提供改进的抗原稳定性和免疫原性。最近出现了一些令人兴奋的进展，包括临床前证据表明该策略可能适用于开发创新的新疫苗，例如预防流感、人类免疫缺陷病毒和呼吸道合胞病毒。在这里，我们对展示该领域潜力的关键数据进行了简要回顾。此外，我们还重点介绍了如何将自组装蛋白纳米颗粒的使用与新兴的结构疫苗学学科有效结合，以最大程度地影响疫苗抗原的合理设计。
For over 100 years, vaccines have been one of the most effective medical interventions for reducing infectious disease, and are estimated to save millions of lives globally each year. Nevertheless, many diseases are not yet preventable by vaccination. This large unmet medical need demands further research and the development of novel vaccines with high efficacy and safety. Compared to the 19th and early 20th century vaccines that were made of killed, inactivated, or live-attenuated pathogens, modern vaccines containing isolated, highly purified antigenic protein subunits are safer but tend to induce lower levels of protective immunity. One strategy to overcome the latter is to design antigen nanoparticles: assemblies of polypeptides that present multiple copies of subunit antigens in well-ordered arrays with defined orientations that can potentially mimic the repetitiveness, geometry, size, and shape of the natural host-pathogen surface interactions. Such nanoparticles offer a collective strength of multiple binding sites (avidity) and can provide improved antigen stability and immunogenicity. Several exciting advances have emerged lately, including preclinical evidence that this strategy may be applicable for the development of innovative new vaccines, for example, protecting against influenza, human immunodeficiency virus, and respiratory syncytial virus. Here, we provide a concise review of a critical selection of data that demonstrate the potential of this field. In addition, we highlight how the use of self-assembling protein nanoparticles can be effectively combined with the emerging discipline of structural vaccinology for maximum impact in the rational design of vaccine antigens.