Applications of synthetic biology in the development of SARS-CoV-2 broad-spectrum vaccines

YUAN Weifeng; ZHAO Yongliang; WU Zhixuan; XU Ke

doi:10.12211/2096-8280.2023-088

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Applications of synthetic biology in the development of SARS-CoV-2 broad-spectrum vaccines

Invited Review | 更新时间：2025-03-20

- Applications of synthetic biology in the development of SARS-CoV-2 broad-spectrum vaccines
- Synthetic Biology Journal Vol. 5, Issue 2, Pages: 369-384(2024)
- 作者机构：
  
  武汉大学病毒学国家重点实验室，泰康生命医学中心，生命科学学院，湖北武汉 430072
- 作者简介：
- 基金信息：
- DOI：10.12211/2096-8280.2023-088
  CLC： Q816
- Received：28 November 2023，
  
  Revised：2024-02-18，
  
  Published：30 April 2024
- 稿件说明：
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袁为锋，赵永亮，吴芷萱，徐可. 合成生物学在新冠病毒广谱疫苗研发中的应用［J］. 合成生物学， 2024， 5（2）： 369-384

YUAN Weifeng， ZHAO Yongliang， WU Zhixuan， XU Ke. Applications of synthetic biology in the development of SARS-CoV-2 broad-spectrum vaccines［J］. Synthetic Biology Journal， 2024， 5（2）： 369-384
袁为锋，赵永亮，吴芷萱，徐可. 合成生物学在新冠病毒广谱疫苗研发中的应用［J］. 合成生物学， 2024， 5（2）： 369-384 DOI： 10.12211/2096-8280.2023-088.

YUAN Weifeng， ZHAO Yongliang， WU Zhixuan， XU Ke. Applications of synthetic biology in the development of SARS-CoV-2 broad-spectrum vaccines［J］. Synthetic Biology Journal， 2024， 5（2）： 369-384 DOI： 10.12211/2096-8280.2023-088.

摘要

新型冠状病毒（SARS-CoV-2）自2019年底引发疫情至今，已经变异出Alpha、Beta、Delta和Omicron等不同谱系。传统疫苗的抗原序列来源于某一自然分离株的原始序列，疫苗迭代速度跟不上病毒变异的速度，导致突破性感染的发生，研发跨谱系的广谱疫苗是预防这类高变异呼吸道病毒的迫切需求。随着合成生物技术的发展，抗原的多价偶联、核心抗原模块的提取、抗原内部保守表位的工程化设计、抗原表位展示技术、计算指导的抗原重构等抗原“再设计”方案得以实现，提高了抗原的免疫原性和广谱性。合成生物学还体现在疫苗产品的生产工艺环节，基因工程表达的疫苗抗原以纳米颗粒、病毒载体、核酸、亚单位的形式，借助细菌、酵母、植物、昆虫或哺乳动物细胞等表达平台进行规模化生产。本文综述了近年来合成生物技术在广谱疫苗（尤其是广谱新冠病毒疫苗）多种设计策略中的应用情况，总结了合成生物技术如何通过反向疫苗学的设计展示全新的共性抗原表位和交叉抗原位点，达到“以不变应万变”的广谱保护效果。本文还讨论了多种广谱疫苗设计策略的应用场景及面临的挑战。基于合成生物技术的马赛克设计策略、保守表位工程化设计策略、计算共识序列策略和新型佐剂策略，结合不同的疫苗技术路线，可提高疫苗的免疫原性、广谱保护性和安全性。这为高变异病毒的疫苗研发提供了合成生物学的新思路。

Abstract

Since the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the end of 2019

it has evolved into different lineages

including Alpha

Beta

Delta

and Omicron. The development of broad-spectrum vaccines has become a necessity for preventing the highly mutated respiratory viruses. Traditional vaccine antigens

originating from prototype strains

cannot cover rapid mutations with these viruses

leading to breakthrough infections. With the development of synthetic biology

new technologies such as multivalent coupling of antigens

reconstructed dominate antigen modules

engineering design of conserved epitopes

epitope display

and computation-guided reconstruction have enabled redesigning antigens to achieve stronger immunogenicity with broader spectrum. The technology of synthetic biology is also applicable in the vaccine production process

such as antigen expression in nanoparticles

viral vectors

nucleic acids

and subunits. This article reviews the applications of synthetic biology technology in developing broad-spectrum vaccines in recent years

particularly for the broad-spectrum SARS-CoV-2 vaccines

and summarizes how to display common antigens and cross-antigenic sites by the reverse vaccinology for the activation of broad-spectrum immune responses against different mutant strains

achieving broad-spectrum vaccine protection effects through “remaining constant in response to ever-changing”. The article also provides a comprehensive comparison of the strengths and limitations of different broad-spectrum vaccine design strategies and discusses challenges to applying synthetic biology in the development of vaccines

offering valuable insights for universal against highly mutation viruses.

关键词

Keywords

references

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