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

合成生物学 ›› 2024, Vol. 5 ›› Issue (2): 353-368.DOI: 10.12211/2096-8280.2023-055

合成生物技术助力纳米颗粒疫苗理性设计时代的到来

马雪璟¹^,², 郭畅³, 华兆琳¹^,²^,³, 侯百东¹^,²^,³

^1.中国科学院生物物理研究所，感染与免疫重点实验室，北京 100101
^2.中国科学院大学，北京 100049
^3.昌平实验室，北京 102206

收稿日期:2023-08-16 修回日期:2023-11-10 出版日期:2024-04-30 发布日期:2024-04-28
通讯作者: 华兆琳,侯百东
作者简介:马雪璟（1995—），女，博士研究生。研究方向为B细胞的分化与纳米颗粒疫苗的免疫机制。E-mail：maxuejing1217@126.com
郭畅（1994—），女，博士后。研究方向为基于病原样抗原疫苗策略的新型疫苗研发。E-mail：guochang201212@126.com
华兆琳（1974—），女，博士，副研究员，教授。研究方向为B细胞细胞活化和记忆细胞等不同细胞分化阶段中的转录调控机制，并以此为理论基础指导纳米颗粒为载体的新型疫苗的研发。 E-mail：zlhua@ibp.ac.cn
侯百东（1971—），男，研究员，教授，博士生导师，昌平实验室（CPNL）领衔科学家。长期从事感染免疫学基础理论研究，在B细胞TLR信号启动抗病毒免疫应答功能、新一代病原样抗原（PLA）疫苗策略研究等方面取得原创性理论突破。E-mail：baidong_hou@ibp.ac.cn
基金资助:
国家自然科学基金(81991495);国家重点研发计划(2019YFA0508901)

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

Xuejing MA¹^,², Chang GUO³, Zhaolin HUA¹^,²^,³, Baidong HOU¹^,²^,³

^1.CAS Key Laboratory of Infection and Immunity，Institute of Biophysics，Chinese Academy of Sciences，Beijing 100101，China
^2.University of Chinese Academy of Sciences，Beijing 100049，China
^3.Changping Laboratory，Beijing 102206，China

Received:2023-08-16 Revised:2023-11-10 Online:2024-04-30 Published:2024-04-28
Contact: Zhaolin HUA, Baidong HOU

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。

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 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. {L-End}

Key words: nanoparticles, vaccines, synthetic biology, immune responses, 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, 2024, 5(2): 353-368.

Xuejing MA, Chang GUO, Zhaolin HUA, Baidong HOU. Dawn of the rational design of nanoparticle vaccines aided by the advance of synthetic biology techniques[J]. Synthetic Biology Journal, 2024, 5(2): 353-368.

图/表 3

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项目	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

项目	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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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

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