a Department of Microbiology and Immunology , University of Melbourne, at The Peter Doherty Institute for Infection and Immunity , Melbourne , Australia.
b ARC Centre for Excellence in Convergent Bio-Nano Science and Technology , University of Melbourne , Parkville , Australia.
Expert Rev Vaccines. 2019 Mar;18(3):269-280. doi: 10.1080/14760584.2019.1578216. Epub 2019 Feb 14.
Immunization has been a remarkably successful public health intervention; however, new approaches to vaccine design are essential to counter existing and emerging infectious diseases which have defied traditional vaccination efforts to date. Nanoparticles (ordered structures with dimensions in the range of 1-1000 nm) have great potential to supplement traditional vaccines based upon pathogen subunits, or killed or attenuated microorganisms, as exemplified by the successful licensure of virus-like particle vaccines for human papillomavirus and hepatitis B. However, the immunological mechanisms that underpin the potent immunity of nanoparticle vaccines are poorly defined.
Here, we review the immunity of nanoparticle immunization. The display of antigen in a repetitive, ordered array mimics the surface of a pathogen, as does their nanoscale size. These properties facilitate enhanced innate immune activation, improved drainage and retention in lymph nodes, stronger engagement with B cell receptors, and augmented T cell help in driving B cell activation.
In the near future, increasingly complex nanoparticle vaccines displaying multiple antigens and/or co-delivered adjuvants will reach clinical trials. An improved mechanistic understanding of nanoparticle vaccination will ultimately facilitate the rational design of improved vaccines for human health.
免疫接种是一项非常成功的公共卫生干预措施;然而,为了应对目前和新出现的传染病,有必要采取新的疫苗设计方法,而这些传染病迄今一直令传统的疫苗接种工作受挫。纳米颗粒(尺寸在 1-1000nm 范围内的有序结构)具有很大的潜力来补充基于病原体亚单位或已杀死或减毒的微生物的传统疫苗,例如已成功获得用于人乳头瘤病毒和乙型肝炎的病毒样颗粒疫苗的许可。然而,纳米颗粒疫苗产生强大免疫力的免疫机制还没有得到很好的定义。
在这里,我们回顾了纳米颗粒免疫接种的免疫。抗原以重复的、有序的方式展示,类似于病原体的表面,纳米级的大小也是如此。这些特性促进了先天免疫的增强激活,改善了在淋巴结中的引流和保留,增强了与 B 细胞受体的结合,并增强了 T 细胞对 B 细胞激活的辅助作用。
在不久的将来,将有越来越复杂的展示多种抗原和/或共同递呈佐剂的纳米颗粒疫苗进入临床试验。对纳米颗粒接种的机制有了更好的理解,最终将有助于为人类健康设计出更好的疫苗。