合成生物学在新冠病毒广谱疫苗研发中的应用

袁为锋; 赵永亮; 吴芷萱; 徐可

doi:10.12211/2096-8280.2023-088

您当前的位置：

首页 >

文章列表页 >

合成生物学在新冠病毒广谱疫苗研发中的应用

特约评述 | 更新时间：2025-03-20

- 合成生物学在新冠病毒广谱疫苗研发中的应用
- Applications of synthetic biology in the development of SARS-CoV-2 broad-spectrum vaccines
- 合成生物学 2024年5卷第2期页码：369-384
- 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：
  
  [ "袁为锋（1995—），男，博士后。研究方向为病毒宿主相互作用与抗病毒药物的靶点发现、新型流感/冠状病毒疫苗研发。E-mail：ywf519@whu.edu.cn" ]
  [ "徐可（1982—），女，教授，博士生导师。研究方向为呼吸道RNA病毒分子致病机制、呼吸道病毒共感染、抗呼吸道RNA病毒广谱药物靶标发现、广谱疫苗研发等。E-mail：xuke03@whu.edu.cn" ]
- 基金信息：
  
  国家重点研发计划(2023YFC2307800);湖北省支持企业技术创新发展项目(2021BAB117);武汉大学示范课堂建设项目(2022ZG090)
- DOI：10.12211/2096-8280.2023-088
  中图分类号： Q816
- 收稿：2023-11-28，
  
  修回：2024-02-18，
  
  纸质出版：2024-04-30
- 稿件说明：
移动端阅览
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

WILHELM A , WIDERA M , GRIKSCHEIT K , et al . Limited neutralisation of the SARS-CoV-2 Omicron subvariants BA.1 and BA.2 by convalescent and vaccine serum and monoclonal antibodies [J ] . EBioMedicine , 2022 , 82 : 104158 .

CAO Y L , YISIMAYI A , JIAN F C , et al . BA.2.12.1, BA.4 and BA.5 escape antibodies elicited by Omicron infection [J ] . Nature , 2022 , 608 ( 7923 ): 593 - 602 .

DAI L P , GAO G F . Viral targets for vaccines against COVID-19 [J ] . Nature Reviews Immunology , 2021 , 21 ( 2 ): 73 - 82 .

COSTA CLEMENS S A , WECKX L , CLEMENS R , et al . Heterologous versus homologous COVID-19 booster vaccination in previous recipients of two doses of CoronaVac COVID-19 vaccine in Brazil (RHH-001): a phase 4, non-inferiority, single blind, randomised study [J ] . Lancet , 2022 , 399 ( 10324 ): 521 - 529 .

KAABI N A , ZHANG Y T , XIA S L , et al . Effect of 2 inactivated SARS-CoV-2 vaccines on symptomatic COVID-19 infection in adults: a randomized clinical trial [J ] . JAMA , 2021 , 326 ( 1 ): 35 - 45 .

ELLA R , REDDY S , BLACKWELDER W , et al . Efficacy, safety, and lot-to-lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): interim results of a randomised, double-blind, controlled, phase 3 trial [J ] . Lancet , 2021 , 398 ( 10317 ): 2173 - 2184 .

KHAIRULLIN B , ZAKARYA K , ORYNBAYEV M , et al . Efficacy and safety of an inactivated whole-virion vaccine against COVID-19, QazCovid-in ® , in healthy adults: a multicentre, randomised, single-blind, placebo-controlled phase 3 clinical trial with a 6-month follow-up [J ] . EClinicalMedicine , 2022 , 50 : 101526 .

WALLS A C , FIALA B , SCHÄFER A , et al . Elicitation of potent neutralizing antibody responses by designed protein nanoparticle vaccines for SARS-CoV-2 [EB/OL ] . BioRxiv , 2020 : 2020 . 08 . 11 . 247395 [ 2023-08-01 ] . https://www.biorxiv.org/content/10.1101/2020.08.11.247395v1 https://www.biorxiv.org/content/10.1101/2020.08.11.247395v1 .

WEIDENBACHER P A , SANYAL M , FRIEDLAND N , et al . A ferritin-based COVID-19 nanoparticle vaccine that elicits robust, durable, broad-spectrum neutralizing antisera in non-human primates [J ] . Nature Communications , 2023 , 14 ( 1 ): 2149 .

RAHIKAINEN R , RIJAL P , TAN T K , et al . Overcoming symmetry mismatch in vaccine nanoassembly through spontaneous amidation [J ] . Angewandte Chemie International Edition , 2021 , 60 ( 1 ): 321 - 330 .

KANG Y F , SUN C , ZHUANG Z , et al . Rapid development of SARS-CoV-2 spike protein receptor-binding domain self-assembled nanoparticle vaccine candidates [J ] . ACS Nano , 2021 , 15 ( 2 ): 2738 - 2752 .

ÁÑEZ G , DUNKLE L M , GAY C L , et al . Safety, immunogenicity, and efficacy of the NVX-CoV2373 COVID-19 vaccine in adolescents: a randomized clinical trial [J ] . JAMA Network Open , 2023 , 6 ( 4 ): e239135 .

LI L , HONDA-OKUBO Y , BALDWIN J , et al . Covax-19/Spikogen® vaccine based on recombinant spike protein extracellular domain with Advax-CpG55.2 adjuvant provides single dose protection against SARS-CoV-2 infection in hamsters [J ] . Vaccine , 2022 , 40 ( 23 ): 3182 - 3192 .

BRAVO L , SMOLENOV I , HAN H H , et al . Efficacy of the adjuvanted subunit protein COVID-19 vaccine, SCB-2019: a phase 2 and 3 multicentre, double-blind, randomised, placebo-controlled trial [J ] . Lancet , 2022 , 399 ( 10323 ): 461 - 472 .

ZHAO X , ZHANG R , QIAO S T , et al . Omicron SARS-CoV-2 neutralization from inactivated and ZF2001 vaccines [J ] . The New England Journal of Medicine , 2022 , 387 ( 3 ): 277 - 280 .

CHAPPELL K J , MORDANT F L , LI Z Y , et al . Safety and immunogenicity of an MF59-adjuvanted spike glycoprotein-clamp vaccine for SARS-CoV-2: a randomised, double-blind, placebo-controlled, phase 1 trial [J ] . The Lancet Infectious Diseases , 2021 , 21 ( 10 ): 1383 - 1394 .

WANG G Q , ZHAO K X , HAN J , et al . Safety and immunogenicity of a bivalent SARS-CoV-2 recombinant protein vaccine, SCTV01C in unvaccinated adults: a randomized, double-blinded, placebo-controlled, phase Ⅰ clinical trial [J ] . The Journal of Infection , 2023 , 86 ( 2 ): 154 - 225 .

HSIEH S M , LIU M C , CHEN Y H , et al . Safety and immunogenicity of CpG 1018 and aluminium hydroxide-adjuvanted SARS-CoV-2 S-2P protein vaccine MVC-COV1901: interim results of a large-scale, double-blind, randomised, placebo-controlled phase 2 trial in Taiwan [J ] . The Lancet Respiratory Medicine , 2021 , 9 ( 12 ): 1396 - 1406 .

EUGENIA-TOLEDO-ROMANÍ M , VERDECIA-SÁNCHEZ L , RODRÍGUEZ-GONZÁLEZ M , et al . Safety and immunogenicity of anti-SARS CoV-2 vaccine SOBERANA 02 in homologous or heterologous scheme: open label phase Ⅰ and phase Ⅱa clinical trials [J ] . Vaccine , 2022 , 40 ( 31 ): 4220 - 4230 .

SADOFF J , GRAY G , VANDEBOSCH A , et al . Safety and efficacy of single-dose Ad26.COV2.S vaccine against covid-19 [J ] . The New England Journal of Medicine , 2021 , 384 ( 23 ): 2187 - 2201 .

SOLTANI S , MATIN B K , GOUYA M M , et al . A prospective cohort study protocol: monitoring and surveillance of adverse events following heterologous booster doses of Oxford AstraZeneca COVID-19 vaccine in previous recipients of two doses of Sinopharm or Sputnik Ⅴ vaccines in Iran [J ] . BMC Public Health , 2023 , 23 ( 1 ): 1415 .

LI J X , WU S P , GUO X L , et al . Safety and immunogenicity of heterologous boost immunisation with an orally administered aerosolised Ad5-nCoV after two-dose priming with an inactivated SARS-CoV-2 vaccine in Chinese adults: a randomised, open-label, single-centre trial [J ] . The Lancet Respiratory Medicine , 2022 , 10 ( 8 ): 739 - 748 .

RAMASAMY M N , KELLY E J , SEEGOBIN S , et al . Immunogenicity and safety of AZD2816, a beta (B.1.351) variant COVID-19 vaccine, and AZD1222 (ChAdOx1 nCoV-19) as third-dose boosters for previously vaccinated adults: a multicentre, randomised, partly double-blinded, phase 2/3 non-inferiority immunobridging study in the UK and Poland [J ] . The Lancet Microbe , 2023 , 4 ( 11 ): e863 - e874 .

ZHU F C , HUANG S J , LIU X H , et al . Safety and efficacy of the intranasal spray SARS-CoV-2 vaccine dNS1-RBD: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial [J ] . The Lancet Respiratory Medicine , 2023 , 11 ( 12 ): 1075 - 1088 .

THOMAS S J , MOREIRA E D , KITCHIN N , et al . Safety and efficacy of the BNT162b2 mRNA covid-19 vaccine through 6 months [J ] . The New England Journal of Medicine , 2021 , 385 ( 19 ): 1761 - 1773 .

TSENG H F , ACKERSON B K , SY L S , et al . mRNA-1273 bivalent (original and Omicron ) COVID-19 vaccine effectiveness against COVID-19 outcomes in the United States [J ] . Nature Communications , 2023 , 14 ( 1 ): 5851 .

CHEN G L , LI X F , DAI X H , et al . Safety and immunogenicity of the SARS-CoV-2 ARCoV mRNA vaccine in Chinese adults: a randomised, double-blind, placebo-controlled, phase 1 trial [J ] . The Lancet Microbe , 2022 , 3 ( 3 ): e193 - e202 .

KHOBRAGADE A , BHATE S , RAMAIAH V , et al . Efficacy, safety, and immunogenicity of the DNA SARS-CoV-2 vaccine (ZyCoV-D): the interim efficacy results of a phase 3, randomised, double-blind, placebo-controlled study in India [J ] . Lancet , 2022 , 399 ( 10332 ): 1313 - 1321 .

QU D , ZHENG B J , YAO X , et al . Intranasal immunization with inactivated SARS-CoV (SARS-associated coronavirus) induced local and serum antibodies in mice [J ] . Vaccine , 2005 , 23 ( 7 ): 924 - 931 .

NEUMANN G , FUJII K , KINO Y , et al . An improved reverse genetics system for influenza A virus generation and its implications for vaccine production [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2005 , 102 ( 46 ): 16825 - 16829 .

TLAXCA J L , ELLIS S , REMMELE R L JR . Live attenuated and inactivated viral vaccine formulation and nasal delivery: potential and challenges [J ] . Advanced Drug Delivery Reviews , 2015 , 93 : 56 - 78 .

LIU Y , ZHANG X W , LIU J Y , et al . A live-attenuated SARS-CoV-2 vaccine candidate with accessory protein deletions [J ] . Nature Communications , 2022 , 13 ( 1 ): 4337 .

YE Z W , ONG C P , TANG K M , et al . Intranasal administration of a single dose of a candidate live attenuated vaccine derived from an NSP16-deficient SARS-CoV-2 strain confers sterilizing immunity in animals [J ] . Cellular & Molecular Immunology , 2022 , 19 ( 5 ): 588 - 601 .

JEYANATHANM , AFKHAMIS , SMAILLF , et al . Immunological considerations for COVID-19 vaccine strategies [J ] . Nature Reviews Immunology , 2020 , 20 ( 10 ): 615 - 632 .

WARD B J , GOBEIL P , SÉGUIN A , et al . Phase 1 randomized trial of a plant-derived virus-like particle vaccine for COVID-19 [J ] . Nature Medicine , 2021 , 27 ( 6 ): 1071 - 1078 .

HAGER K J , PÉREZ MARC G , GOBEIL P , et al . Efficacy and safety of a recombinant plant-based adjuvanted COVID-19 vaccine [J ] . The New England Journal of Medicine , 2022 , 386 ( 22 ): 2084 - 2096 .

LI M C , WANG H , TIAN L L , et al . COVID-19 vaccine development: milestones, lessons and prospects [J ] . Signal Transduction and Targeted Therapy , 2022 , 7 ( 1 ): 146 .

GEORGIEV I S , JOYCE M G , CHEN R E , et al . Two-component ferritin nanoparticles for multimerization of diverse trimeric antigens [J ] . ACS Infectious Diseases , 2018 , 4 ( 5 ): 788 - 796 .

ZHANG X , MEINING W , FISCHER M , et al . X-ray structure analysis and crystallographic refinement of lumazine synthase from the hyperthermophile Aquifex aeolicus at 1.6 A resolution: determinants of thermostability revealed from structural comparisons [J ] . Journal of Molecular Biology , 2001 , 306 ( 5 ): 1099 - 1114 .

IZARD T , AEVARSSON A , ALLEN M D , et al . Principles of quasi-equivalence and Euclidean geometry govern the assembly of cubic and dodecahedral cores of pyruvate dehydrogenase complexes [J ] . Proceedings of the National Academy of Sciences of the United States of America , 1999 , 96 ( 4 ): 1240 - 1245 .

CARTER DANIEL C , BRENDA W , GRAY J W , et al . A unique protein self-assembling nanoparticle with significant advantages in vaccine development and production [J ] . Journal of Nanomaterials , 2020 , 2020 : 4297937 .

KARPIŃSKI T M , OŻAROWSKI M , SEREMAK-MROZIKIEWICZ A , et al . The 2020 race towards SARS-CoV-2 specific vaccines [J ] . Theranostics , 2021 , 11 ( 4 ): 1690 - 1702 .

LI Y D , CHI W Y , SU J H , et al . Coronavirus vaccine development: from SARS and MERS to COVID-19 [J ] . Journal of Biomedical Science , 2020 , 27 ( 1 ): 104 .

BHAT E A , KHAN J , SAJJAD N , et al . SARS-CoV-2: insight in genome structure, pathogenesis and viral receptor binding analysis — an updated review [J ] . International Immunopharmacology , 2021 , 95 : 107493 .

WU Y , WANG F R , SHEN C G , et al . A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2 [J ] . Science , 2020 , 368 ( 6496 ): 1274 - 1278 .

HUMPHREYS I R , SEBASTIAN S . Novel viral vectors in infectious diseases [J ] . Immunology , 2018 , 153 ( 1 ): 1 - 9 .

LIU X , LIU C , LIU G , et al . COVID-19: progress in diagnostics, therapy and vaccination [J ] . Theranostics , 2020 , 10 ( 17 ): 7821 - 7835 .

WANG J L , PENG Y , XU H Y , et al . The COVID-19 vaccine race: challenges and opportunities in vaccine formulation [J ] . AAPS PharmSciTech , 2020 , 21 ( 6 ): 225 .

MERCADO N B , ZAHN R , WEGMANN F , et al . Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques [J ] . Nature , 2020 , 586 ( 7830 ): 583 - 588 .

FOLEGATTI P M , EWER K J , ALEY P K , et al . Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial [J ] . Lancet , 2020 , 396 ( 10249 ): 467 - 478 .

CHEN J Y , WANG P , YUAN L Z , et al . A live attenuated virus-based intranasal COVID-19 vaccine provides rapid, prolonged, and broad protection against SARS-CoV-2 [J ] . Science Bulletin , 2022 , 67 ( 13 ): 1372 - 1387 .

KUTZLERM A , WEINERD B . DNA vaccines: ready for prime time? [J ] . Nature Reviews Genetics , 2008 , 9 ( 10 ): 776 - 788 .

PARDI N , HOGAN M J , PORTER F W , et al . mRNA vaccines-a new era in vaccinology [J ] . Nature Reviews Drug Discovery , 2018 , 17 ( 4 ): 261 - 279 .

WANG Z Y , JACOBUS E J , STIRLING D C , et al . Reducing cell intrinsic immunity to mRNA vaccine alters adaptive immune responses in mice [J ] . Molecular Therapy Nucleic Acids , 2023 , 34 : 102045 .

RAUCH S , ROTH N , SCHWENDT K , et al . mRNA-based SARS-CoV-2 vaccine candidate CVnCoV induces high levels of virus-neutralising antibodies and mediates protection in rodents [J ] . NPJ Vaccines , 2021 , 6 ( 1 ): 57 .

KARIKÓ K , BUCKSTEIN M , NI H P , et al . Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA [J ] . Immunity , 2005 , 23 ( 2 ): 165 - 175 .

KARIKÓ K , MURAMATSU H , WELSH F A , et al . Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability [J ] . Molecular Therapy , 2008 , 16 ( 11 ): 1833 - 1840 .

XIA X H . Detailed dissection and critical evaluation of the pfizer/BioNTech and moderna mRNA vaccines [J ] . Vaccines , 2021 , 9 ( 7 ): 734 .

QU L , YI Z Y , SHEN Y , et al . Circular RNA vaccines against SARS-CoV-2 and emerging variants [J ] . Cell , 2022 , 185 ( 10 ): 1728 - 1744.e16 .

LI D P , MARTINEZ D R , SCHÄFER A , et al . Breadth of SARS-CoV-2 neutralization and protection induced by a nanoparticle vaccine [J ] . Nature Communications , 2022 , 13 ( 1 ): 6309 .

ZHANG Z R , HE Q R , ZHAO W , et al . A heterologous V-01 or variant-matched bivalent V-01D-351 booster following primary series of inactivated vaccine enhances the neutralizing capacity against SARS-CoV-2 Delta and Omicron strains [J ] . Journal of Clinical Medicine , 2022 , 11 ( 14 ): 4164 .

ZHAO Y L , NI W J , LIANG S M , et al . Vaccination with S pan , an antigen guided by SARS-CoV-2 S protein evolution, protects against challenge with viral variants in mice [J ] . Science Translational Medicine , 2023 , 15 ( 677 ): eabo3332 .

KANG Y F , SUN C , SUN J , et al . Quadrivalent mosaic HexaPro-bearing nanoparticle vaccine protects against infection of SARS-CoV-2 variants [J ] . Nature Communications , 2022 , 13 ( 1 ): 2674 .

JOYCE M G , KING H A D , ELAKHAL-NAOUAR I , et al . A SARS-CoV-2 ferritin nanoparticle vaccine elicits protective immune responses in nonhuman primates [J ] . Science Translational Medicine , 2022 , 14 ( 632 ): eabi5735 .

TAI W B , CHAI B J , FENG S Y , et al . Development of a ferritin-based nanoparticle vaccine against the SARS-CoV-2 Omicron variant [J ] . Signal Transduction and Targeted Therapy , 2022 , 7 ( 1 ): 173 .

PAN X Y , SHI J , HU X , et al . RBD-homodimer, a COVID-19 subunit vaccine candidate, elicits immunogenicity and protection in rodents and nonhuman primates [J ] . Cell Discovery , 2021 , 7 ( 1 ): 82 .

DAI L P , DUAN H X , LIU X Y , et al . Omicron neutralisation: RBD-dimer booster versus BF.7 and BA.5.2 breakthrough infection [J ] . Lancet , 2023 , 402 ( 10403 ): 687 - 689 .

JOYCE M G , CHEN W H , SANKHALA R S , et al . SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity [J ] . Cell Reports , 2021 , 37 ( 12 ): 110143 .

Jr MOREIRA E D , KITCHIN N , XU X , et al . Safety and efficacy of a third dose of BNT162b2 COVID-19 vaccine [J ] . The New England Journal of Medicine , 2022 , 386 ( 20 ): 1910 - 1921 .

DAI L P , ZHENG T Y , XU K , et al . A universal design of betacoronavirus vaccines against COVID-19, MERS, and SARS [J ] . Cell , 2020 , 182 ( 3 ): 722 - 733.e11 .

WANG R , HUANG X , CAO T S , et al . Development of a thermostable SARS-CoV-2 variant-based bivalent protein vaccine with cross-neutralizing potency against Omicron subvariants [J ] . Virology , 2022 , 576 : 61 - 68 .

WANG R , HUANG H P , YU C L , et al . A spike-trimer protein-based tetravalent COVID-19 vaccine elicits enhanced breadth of neutralization against SARS-CoV-2 Omicron subvariants and other variants [J ] . Science China Life Sciences , 2023 , 66 ( 8 ): 1818 - 1830 .

WRAPP D , WANG N S , CORBETT K S , et al . Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation [J ] . Science , 2020 , 367 ( 6483 ): 1260 - 1263 .

SUN X Y , YI C Y , ZHU Y F , et al . Neutralization mechanism of a human antibody with pan-coronavirus reactivity including SARS-CoV-2 [J ] . Nature Microbiology , 2022 , 7 ( 7 ): 1063 - 1074 .

MA X C , ZOU F , YU F , et al . Nanoparticle vaccines based on the receptor binding domain (RBD) and heptad repeat (HR) of SARS-CoV-2 elicit robust protective immune responses [J ] . Immunity , 2020 , 53 ( 6 ): 1315 - 1330.e9 .

PANG W , LU Y , ZHAO Y B , et al . A variant-proof SARS-CoV-2 vaccine targeting HR1 domain in S2 subunit of spike protein [J ] . Cell Research , 2022 , 32 ( 12 ): 1068 - 1085 .

WANG X L , SUN L J , LIU Z Z , et al . An engineered recombinant protein containing three structural domains in SARS-CoV-2 S2 protein has potential to act as a pan-human coronavirus entry inhibitor or vaccine antigen [J ] . Emerging Microbes & Infections , 2023 , 12 ( 2 ): 2244084 .

YU D W , ZHU Y M , YAN H X , et al . Pan-coronavirus fusion inhibitors possess potent inhibitory activity against HIV-1, HIV-2, and Simian immunodeficiency virus [J ] . Emerging Microbes & Infections , 2021 , 10 ( 1 ): 810 - 821 .

BENHAIM M A , MANGALA PRASAD V , GARCIA N K , et al . Structural monitoring of a transient intermediate in the hemagglutinin fusion machinery on influenza virions [J ] . Science Advances , 2020 , 6 ( 18 ): eaaz8822 .

LADINSKY M S , GNANAPRAGASAM P N , YANG Z , et al . Electron tomography visualization of HIV-1 fusion with target cells using fusion inhibitors to trap the pre-hairpin intermediate [J ] . eLife , 2020 , 9 : e58411 .

DOLGIN E . Pan-coronavirus vaccine pipeline takes form [J ] . Nature Reviews Drug Discovery , 2022 , 21 ( 5 ): 324 - 326 .

WU Y T , WANG S J , ZHANG Y L , et al . Lineage-mosaic and mutation-patched spike proteins for broad-spectrum COVID-19 vaccine [J ] . Cell Host & Microbe , 2022 , 30 ( 12 ): 1732 - 1744.e7 .

RICE A , VERMA M , SHIN A , et al . Intranasal plus subcutaneous prime vaccination with a dual antigen COVID-19 vaccine elicits T-cell and antibody responses in mice [J ] . Scientific Reports , 2021 , 11 ( 1 ): 14917 .

STERNKE M , TRIPP K W , BARRICK D . Consensus sequence design as a general strategy to create hyperstable, biologically active proteins [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2019 , 116 ( 23 ): 11275 - 11284 .

TEBAS P , ROBERTS C C , MUTHUMANI K , et al . Safety and immunogenicity of an anti-Zika virus DNA vaccine [J ] . The New England Journal of Medicine , 2021 , 385 ( 12 ): e35 .

WANG R , ZHENG X Y , SUN J , et al . Vaccination with a single consensus envelope protein ectodomain sequence administered in a heterologous regimen induces tetravalent immune responses and protection against dengue viruses in mice [J ] . Frontiers in Microbiology , 2019 , 10 : 1113 .

CHEN M W , CHENG T J , HUANG Y X , et al . A consensus-hemagglutinin-based DNA vaccine that protects mice against divergent H5N1 influenza viruses [J ] . Proceedings of the National Academy of Sciences of the United States of America , 2008 , 105 ( 36 ): 13538 - 13543 .

ELLIOTT S T C , KEATON A A , CHU J D , et al . A synthetic micro-consensus DNA vaccine generates comprehensive influenza A H3N2 immunity and protects mice against lethal challenge by multiple H3N2 viruses [J ] . Human Gene Therapy , 2018 , 29 ( 9 ): 1044 - 1055 .

PING X Q , HU W B , XIONG R , et al . Generation of a broadly reactive influenza H1 antigen using a consensus HA sequence [J ] . Vaccine , 2018 , 36 ( 32 Pt B ): 4837 - 4845 .

LIU Z Z , XU W , XIA S , et al . RBD-Fc-based COVID-19 vaccine candidate induces highly potent SARS-CoV-2 neutralizing antibody response [J ] . Signal Transduction and Targeted Therapy , 2020 , 5 ( 1 ): 282 .

SUN S Y , CAI Y Q , SONG T Z , et al . Interferon-armed RBD dimer enhances the immunogenicity of RBD for sterilizing immunity against SARS-CoV-2 [J ] . Cell Research , 2021 , 31 ( 9 ): 1011 - 1023 .

LIU Z Z , ZHOU J , XU W , et al . A novel STING agonist-adjuvanted pan-sarbecovirus vaccine elicits potent and durable neutralizing antibody and T cell responses in mice, rabbits and NHPs [J ] . Cell Research , 2022 , 32 ( 3 ): 269 - 287 .

WANG J , LI P Y , YU Y , et al . Pulmonary surfactant-biomimetic nanoparticles potentiate heterosubtypic influenza immunity [J ] . Science , 2020 , 367 ( 6480 ): eaau0810 .

LIU Z Z , XU W , CHEN Z G , et al . An ultrapotent pan-β- coronavirus lineage B (β-CoV-B) neutralizing antibody locks the receptor-binding domain in closed conformation by targeting its conserved epitope [J ] . Protein & Cell , 2022 , 13 ( 9 ): 655 - 675 .

HEATH P T , GALIZA E P , BAXTER D N , et al . Safety and efficacy of NVX-CoV2373 COVID-19 vaccine [J ] . The New England Journal of Medicine , 2021 , 385 ( 13 ): 1172 - 1183 .

LAZARUS R , QUERTON B , CORBIC RAMLJAK I , et al . Immunogenicity and safety of an inactivated whole-virus COVID-19 vaccine (VLA2001) compared with the adenoviral vector vaccine ChAdOx1-S in adults in the UK (COV-COMPARE): interim analysis of a randomised, controlled, phase 3, immunobridging trial [J ] . The Lancet Infectious Diseases , 2022 , 22 ( 12 ): 1716 - 1727 .

LIU Y , DAI L P , FENG X L , et al . Fast and long-lasting immune response to S-trimer COVID-19 vaccine adjuvanted by PIKA [J ] . Molecular Biomedicine , 2021 , 2 ( 1 ): 29 .

XU K J , YU S Y , WANG K , et al . AI and knowledge-based method for rational design of Escherichia coli Sigma70 promoters [J ] . ACS Synthetic Biology , 2024 , 13 ( 1 ): 402 - 407 .

LAI C J , KIM D , KANG S , et al . Viral codon optimization on SARS-CoV-2 spike boosts immunity in the development of COVID-19 mRNA vaccines [J ] . Journal of Medical Virology , 2023 , 95 ( 10 ): e29183 .

BEUKERS M W , KLAASSEN C H , DE GRIP W J , et al . Heterologous expression of rat epitope-tagged histamine H 2 receptors in insect Sf9 cells [J ] . British Journal of Pharmacology , 1997 , 122 ( 5 ): 867 - 874 .

DENG S F , LIU Y , TAM R C , et al . An intranasal influenza virus-vectored vaccine prevents SARS-CoV-2 replication in respiratory tissues of mice and hamsters [J ] . Nature Communications , 2023 , 14 ( 1 ): 2081 .

ZHANG H , ZHANG L , LIN A , et al . Algorithm for optimized mRNA design improves stability and immunogenicity [J ] . Nature , 2023 , 621 ( 7978 ): 396 - 403 .

SADEGHALVAD M , MANSOURABADI A H , NOORI M , et al . Recent developments in SARS-CoV-2 vaccines: a systematic review of the current studies [J ] . Reviews in Medical Virology , 2023 , 33 ( 1 ): e2359 .

KORBER B , FISCHER W M , GNANAKARAN S , et al . Tracking changes in SARS-CoV-2 spike: evidence that D614G increases infectivity of the COVID-19 virus [J ] . Cell , 2020 , 182 ( 4 ): 812 - 827.e19 .

GARCIA-BELTRAN W F , LAM E C , DENIS K S , et al . Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity [J ] . Cell , 2021 , 184 ( 9 ): 2523 .

CELE S , JACKSON L , KHOURY D S , et al . Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization [J ] . Nature , 2022 , 602 ( 7898 ): 654 - 656 .

GRETEBECK L M , SUBBARAO K . Animal models for SARS and MERS coronaviruses [J ] . Current Opinion in Virology , 2015 , 13 : 123 - 129 .

VAN DOREMALEN N , MUNSTER V J . Animal models of Middle East respiratory syndrome coronavirus infection [J ] . Antiviral Research , 2015 , 122 : 28 - 38 .

HOFFMANN M , KLEINE-WEBER H , SCHROEDER S , et al . SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor [J ] . Cell , 2020 , 181 ( 2 ): 271 - 280.e8 .

BAO L L , DENG W , HUANG B Y , et al . The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice [J ] . Nature , 2020 , 583 ( 7818 ): 830 - 833 .

SILVAS J A , VASQUEZ D M , PARK J G , et al . Contribution of SARS-CoV-2 accessory proteins to viral pathogenicity in K18 human ACE2 transgenic mice [J ] . Journal of Virology , 2021 , 95 ( 17 ): e0040221 .

SUN J , ZHUANG Z , ZHENG J , et al . Generation of a broadly useful model for COVID-19 pathogenesis, vaccination, and treatment [J ] . Cell , 2020 , 182 ( 3 ): 734 - 743.e5 .

KIM Y I , KIM S G , KIM S M , et al . Infection and rapid transmission of SARS-CoV-2 in ferrets [J ] . Cell Host & Microbe , 2020 , 27 ( 5 ): 704 - 709.e2 .

LI D P , EDWARDS R J , MANNE K , et al . The functions of SARS-CoV-2 neutralizing and infection-enhancing antibodies in vitro and in mice and nonhuman Primates [EB/OL ] . bioRxiv , 2021 : 2020 . 12 . 31 . 424729 [ 2023-11-01 ] . https://www.biorxiv.org/content/10.1101/2020.12.31.424729v2 https://www.biorxiv.org/content/10.1101/2020.12.31.424729v2 .

CHANDRASHEKAR A , LIU J Y , MARTINOT A J , et al . SARS-CoV-2 infection protects against rechallenge in rhesus macaques [J ] . Science , 2020 , 369 ( 6505 ): 812 - 817 .

BUTT A A , GUERRERO M D , CANLAS E B , et al . Evaluation of mortality attributable to SARS-CoV-2 vaccine administration using national level data from Qatar [J ] . Nature Communications , 2023 , 14 ( 1 ): 24 .

MULRONEY T E , PÖYRY T , YAM-PUC J C , et al . N 1 -methylpseudouridylation of mRNA causes +1 ribosomal frameshifting [J ] . Nature , 2024 , 625 ( 7993 ): 189 - 194 .

WOO E J , MBA-JONAS A , DIMOVA R B , et al . Association of receipt of the Ad26.COV2.S COVID-19 vaccine with presumptive guillain-barré syndrome, february-july 2021 [J ] . JAMA , 2021 , 326 ( 16 ): 1606 - 1613 .

GREINACHER A , THIELE T , WARKENTIN T E , et al . Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination [J ] . The New England Journal of Medicine , 2021 , 384 ( 22 ): 2092 - 2101 .

浏览量

下载量

CSCD

文章被引用时，请邮件提醒。

提交

工具集

关联资源

蛋白质优化设计与从头合成引领的疫苗研发革命

合成生物学赋能细胞膜纳米颗粒的精准诊疗

合成生物学策略下的人工血液研究进展

合成生物学在医学诊疗中的应用与伦理治理：技术突破与价值边界

医用聚羟基脂肪酸酯（PHA）的生物合成策略及其在人类健康领域的新进展