合成生物技术助力纳米颗粒疫苗理性设计时代的到来

Dawn of the rational design of nanoparticle vaccines aided by the advance of synthetic biology techniques

纳米颗粒疫苗自1981年首次应用于人体以来,经历逾40年的发展历程,在临床应用方面已取得了极大成功。尤其是在乙型肝炎病毒(hepatitis B virus,HBV)、人乳头瘤病毒(human papillomavirus,HPV)等疫苗领域,纳米颗粒疫苗以显著的免疫原性和良好的安全性在遏制病毒传播和疾病防控方面发挥了不可替代的作用,为人类社会的健康安全作出了巨大贡献。自新型冠状病毒疫情爆发以来,迫切的防控需要进一步推动了包括纳米颗粒疫苗在内的各类新型疫苗技术的发展。然而,由于被相对更经验化的设计方式和更复杂的制备工艺制约,纳米颗粒疫苗临床转化应用的速度并不突出。因此,通过理性设计来提升纳米颗粒疫苗的研制效率和应用范围,正成为其未来发展的重要方向和关键目标。合成生物技术在纳米颗粒疫苗发展的过程中一直起着重要作用。近年来,新型合成生物技术的应用在推动纳米颗粒平台灵活性方面取得了显著进展,有望满足未来对抗原承载多样性的需求。本文首先综述了纳米颗粒疫苗发展的技术沿革与进展,从抗原自组装形成的纳米颗粒疫苗到抗原协助组装的纳米颗粒疫苗,再到抗原平台展示的纳米颗粒疫苗。其次,总结了纳米颗粒疫苗提高抗原淋巴引流效率、抗原增强B细胞信号活化、抗原具有独特的抗原提呈方式等增强抗原免疫原性的特殊作用。最后概括了纳米颗粒疫苗在新型冠状病毒流行中的转化应用,如新型冠状病毒刺突蛋白三聚体疫苗、协助组装的新冠纳米颗粒疫苗、标签偶联展示的新冠纳米颗粒疫苗。随着对免疫应答机理的深入研究和对抗原提呈新规律的发现,利用合成生物技术也将有助于充分发掘纳米颗粒疫苗的独特免疫功能、满足高难度疫苗研制的要求。因此有理由相信:在合成生物技术助力下,未来纳米颗粒疫苗将在新突发及重大传染性疾病的防控中做出更突出的贡献。

Nanoparticle vaccines have been established firmly as a cornerstone of modern immunization strategies,with a compelling history that trace their pioneering use in human being back to 1981.Within the past four decades,these vaccines have not only demonstrated their efficacy,but have also been developed as powerful tools in fighting against a range of infectious diseases,most notably hepatitis B virus(HBV)and human papillomavirus(HPV).Their success can be attributed to their exceptional immunogenicity and impeccable safety as well,making them invaluable in curbing the spread of viruses and safeguarding the health and well-being of human being.The global outbreaks of the COVID-19 pandemic,driven by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has made vaccination into the forefront of public health priorities.This unprecedent challenge has accelerated the progress of various vaccine technologies,with nanoparticle vaccines attracting considerable attention.However,due to their relatively empirical design approaches and complicated manufacturing processes,progress in the clinical trials of SARS-CoV-2 nanoparticle vaccines has not been highlighted particularly.Therefore,the imperative for developing nanoparticle vaccines is to figure out their rational design,requiring groundbreaking advancement in novel technologies and theories.In this endeavor,synthetic biotechnology has emerged as an indispensable tool,driving the technological innovations of the production of nanoparticle vaccines.This article begins with an overview of technological advancements in the development of nanoparticle vaccines,encompassing progress from self-assembled nanoparticles to assist-assembled nanoparticles,and ultimately to antigen-display on formed nanoparticles.Furthermore,discoveries in understanding the unique roles of nanoparticle vaccines in enhancing antigen immunogenicity are updated,particularly in the function of nanoparticles with novel antigen presentation pathways.Finally,a comprehensive summary of the clinical trials of nanoparticle vaccines on fighting the COVID-19 pandemic is presented.In conclusion,we firmly believe that nanoparticle vaccines,bolstered by the scaffolding of synthetic biotechnology,are poised to emerge as steadfast guardians in the global battle against emerging and highly infectious diseases,and ongoing progress in this regard not only holds great promise,but also has potentials to revolutionize contagious disease prevention and control on a global scale.