合成生物技术助力纳米颗粒疫苗理性设计时代的到来

doi:10.12211/2096-8280.2023-055

摘要/Abstract

摘要：

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扮演着重要作用。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的防控中做出更突出的贡献。

关键词: 纳米颗粒, 疫苗, 合成生物学, 免疫应答, 抗原提呈, 新型冠状病毒肺炎

Abstract:

Nanoparticle vaccines have firmly established themselves as a cornerstone of modern immunization strategies, with a compelling history that traces its origins back to their pioneering use in humans in 1981. Over the course of more than four decades, these vaccines have not only demonstrated their efficacy but have also evolved into powerful tools in the fight against a range of infectious diseases, most notably hepatitis B virus (HBV) and human papillomavirus (HPV). Their success can be attributed to their remarkable combination of exceptional immunogenicity and impeccable safety, making them invaluable in curbing the spread of viruses and safeguarding the health and well-being of society. The eruption of the global COVID-19 pandemic, driven by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has catapulted vaccination into the forefront of public health priorities. This unparalleled challenge has accelerated the progress of various vaccine technologies, with nanoparticle vaccines attracting considerable attention. However, due to their relatively empirical design approach and complicated manufacturing process, progress in the clinical translation of SARS-CoV-2 nanoparticle vaccines has not been particularly prominent. Therefore, the imperative for the field is to chart a course towards rational design, requiring groundbreaking advancements in novel technologies and theories. This imperative, far from being a mere direction, stands as a pivotal objective that shapes the future of nanoparticle vaccine development. In this endeavor, synthetic biotechnology has emerged as an indispensable ally, propelling the technological evolution of these innovative vaccines. This article begins by offering an overview of the technological evolution and advancements in the development of nanoparticle vaccines, encompassing the progression from self-assembled nanoparticles to assist-assembled nanoparticles, and ultimately to antigen-displayed on formed nanoparticle platforms. Additionally, it gives a concise update of new discovery in understanding the distinct roles of nanoparticle vaccines in enhancing antigen immunogenicity, particularly in the function of nanoparticle to utilize a novel antigen presentation pathway. Lastly, it presents a comprehensive summary of the clinical translations of nanoparticle vaccines harnessing the above technology and theory in the context of the COVID-19 pandemic. Overall, this review aims to provide an up-to-date report on the significant strides of synthetic biotechnology in enhancing the flexibility and adaptability of nanoparticle platforms, bringing them into closer alignment with the evolving requirements of diverse antigen carriers. In addition, the in-depth exploration of immune response mechanisms and the revelation of novel antigen presentation pathways, facilitated by synthetic biotechnology, holding the promise to unveil previously concealed dimensions of nanoparticle vaccine immunogenicity. These advancements hold the key for overcoming the challenges posed by the development of high-complexity vaccines. In conclusion, we hold a firm conviction 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. Their ongoing progress not only holds great promise but also has the potential to usher in a transformative era of disease prevention and control on a global scale.

Key words: nanoparticle, vaccine, synthetic biology, immune response, antigen presentation, COVID-19

中图分类号:

Q816

马雪璟, 郭畅, 华兆琳, 侯百东. 合成生物技术助力纳米颗粒疫苗理性设计时代的到来[J]. 合成生物学, DOI: 10.12211/2096-8280.2023-055.

Xuejing Ma, Chang Guo, Zhaolin Hua, Baidong Hou. The dawn of rational design of nanoparticle vaccines aided by the advance of synthetic biology techniques[J]. Synthetic Biology Journal, DOI: 10.12211/2096-8280.2023-055.

图/表 3

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	自组装			协助组装		平台展示
商品名	Nuvaxovid	SCTV01E	CoVLP	VBI-2901/VBI-2902/VBI-2905	GBP510	ABNCoV2	LYB001
开发商	Novavax	Sinoce lltech	Medicao	VBI Vaccines	SK Biosciene	Radboud University	Yantai Patronus Biotech
抗原靶点	S蛋白	S蛋白	S蛋白	S蛋白	RBD蛋白	RBD蛋白	RBD蛋白
佐剂	Matrix-M	SCT-VA02B	AS03	E6020	AS03	MF59	氢氧化铝
接种策略	Day0 + 21	Day0	Day0 + 21	Day0 + 28	Day0 + 28	Day0 + 28	Day0 + 28+56
临床阶段	三期	三期	三期	一期	三期	三期	三期

	自组装			协助组装		平台展示
商品名	Nuvaxovid	SCTV01E	CoVLP	VBI-2901/VBI-2902/VBI-2905	GBP510	ABNCoV2	LYB001
开发商	Novavax	Sinoce lltech	Medicao	VBI Vaccines	SK Biosciene	Radboud University	Yantai Patronus Biotech
抗原靶点	S蛋白	S蛋白	S蛋白	S蛋白	RBD蛋白	RBD蛋白	RBD蛋白
佐剂	Matrix-M	SCT-VA02B	AS03	E6020	AS03	MF59	氢氧化铝
接种策略	Day0 + 21	Day0	Day0 + 21	Day0 + 28	Day0 + 28	Day0 + 28	Day0 + 28+56
临床阶段	三期	三期	三期	一期	三期	三期	三期

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