李晓瑞;李兴航;严汉池;

• 1:天津大学生命科学学院
• 2:武汉生物制品研究所

摘要(Abstract)：

2019年12月发生的新型冠状病毒肺炎(Coronavirus disease 2019,COVID-19)对全球公共卫生造成巨大危机。世界卫生组织(World Health Organization,WHO)在2020年3月11日宣布COVID-19为全球大流行。目前,新型冠状病毒疫苗研发的技术路线主要有灭活疫苗、重组蛋白疫苗、病毒载体疫苗、核酸疫苗和减毒活疫苗,此外,还有运用反向疫苗学和疫苗组学等新兴概念进行疫苗的设计。本文对目前正在研发和临床试验的各类新型冠状病毒疫苗以及研发所面临的挑战作一综述。

关键词(KeyWords)： 2019新型冠状病毒;疫苗研发;新型冠状病毒疫苗

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金（31470731）

作者(Authors): 李晓瑞;李兴航;严汉池;

DOI: 10.13200/j.cnki.cjb.003343

参考文献(References)：

• [1] GAO Q,BAO L,MAO H,et al. Rapid development of an inactivated vaccine for SARS-CoV-2[J]. Science,2020,369(6499):77.
• [2] DHAMA K,SHARUN K,TIWARI R,et al. COVID-19,an emerging coronavirus infection:advances and prospects in designing and developing vaccines,immunotherapeutics,and therapeutics[J]. Hum Vaccin&Immunother,2020,16(6):1232-1238.
• [3] LURIE N,SAVILLE M,HATCHETT R,et al. Developing covid-19 vaccines at pandemic speed[J]. New Engl J Med,2020,382(21):1969-1973.
• [4] WU A P,PENG Y S,HUANG B Y,et al. Genome composition and divergence of the novel coronavirus(2019-n CoV)originating in China[J]. Cell Host Microbe,2020,27(3):325-328.
• [5] CIOTTI M,ANGELETTI S,MINIERI M,et al. COVID-19outbreak:An overview[J]. Chemotherapy,2020,64(5-6):215-223.
• [6] KUBA K,IMAI Y,RAO S A,et al. A crucial role of angiotensin converting enzyme 2(ACE2)in SARS coronavirus-induced lung injury[J]. Nat Med,2005,11(8):875-879.
• [7] VELLOZZI C,BURWEN D R,DOBARDZIC A,et al. Safety of trivalent inactivated influenza vaccines in adults:Background for pandemic influenza vaccine safety monitoring[J]. Vaccine,2009,27(15):2114-2120.
• [8] MURDIN A D,BARRETO L,PLOTKIN S. Inactivated poliovirus vaccine:past and present experience[J]. Vaccine,1996,14(8):735-746.
• [9] ZHOU J,WANG W,ZHONG Q,et al. Immunogenicity,safety,and protective efficacy of an inactivated SARS-associated coronavirus vaccine in rhesus monkeys[J]. Vaccine,2005,23(24):3202-3209.
• [10] DARNELL M E R,PLANT E P,WATANABE H,et al. Severe acute respiratory syndrome coronavirus infection in vaccinated ferrets[J]. J Infect Dis,2007,196(9):1329-1338.
• [11] LIN J T,ZHANG J S,SU N,et al. Safety and immunogenicity from a Phase I trial of inactivated severe acute respiratory syndrome coronavirus vaccine[J]. Antiviral Ther,2007,12(7):1107-1113.
• [12] XIA S,DUAN K,ZHANG Y,et al. Effect of an inactivated vaccine against SARS-CoV-2 on safety and immunogenicity outcomes:Interim analysis of 2 randomized clinical trials[J].JAMA,2020,doi:10.1001/jama.2020.15543.
• [13] Sinovac Biotech Ltd. Sinovac announces positive preliminary results of phase I/II clinical trials for inactivated vaccine candidate against COVID-19[EB/OL].(2020-06-14)[2020-06-16]. http：//www.sinovac.com.cn/?optionid=468&auto_id=1838.
• [14]光明网.中巴合作开展新冠疫苗Ⅲ期临床试验[EB/OL].(2020-06-16)[2020-07-09]. https：//tech.gmw.cn/2020-06/16/content_33915233.htm.
• [15] CALLAWAY E. The race for coronavirus vaccines:a graphical guide[J]. Nature,2020,580(7805):576-577.
• [16] AL-HALIFA S,GAUTHIER L,ARPIN D,et al. Nanoparticlebased vaccines against respiratory viruses[J]. Frontiers Immunol,2019,10. doi:10.3389/fimmu.2019.00022.
• [17] GEOVAX LABS I. GeoVax progresses in coronavirus(COVID-19)vaccine development program[EB/OL].(2020-03-18)[2020-05-20]. https：//www.geovax.com/news/geovax-progresses-in-coronavirus-covid-19-vaccine-development-program.
• [18] WU L,ZHANG Z,GAO H,et al. Open-label phase I clinical trial of Ad5-EBOV in Africans in China[J]. Hum Vaccin&Immunother,2017,13(9):2078-2085.
• [19]人民网.我国已有三个新冠病毒疫苗获批进入临床试验[EB/OL].(2020-04-14)[2020-05-20]. http：//scitech.people.com.cn/n1/2020/0414/c1007-31673366.html.
• [20]康希诺官网.重组新型冠状病毒疫苗（腺病毒载体）II期临床试验计划[EB/OL].(2020-04-09)[2020-4-20]. http：//www.cansinotech.com.cn/uploads/article/attachment/2020/04/20200409/2Tv4sC8Dgj.pdf.
• [21] ZHANG J,XIE B,HASHIMOTO K. Current status of potential therapeutic candidates for the COVID-19 crisis[J]. Brain Behavior Immun,2020,87:59-73.
• [22] ZHU F C,LI Y H,GUAN X H,et al. Safety,tolerability,and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine:a dose-escalation,open-label,non-randomised,first-in-human trial[J]. Lancet(London,England),2020,395(10240):1845-1854.
• [23] HEALTH N I O. NIH clinical trial of investigational vaccine for COVID-19 begins[EB/OL].(2020-03-16)[2020-03-18].https：//www.niaid.nih.gov/news-events/nih-clinical-trialinvestigational-vaccine-covid-19-begins.
• [24] MODERNA I. Moderna advances late-stage development of its vaccine(m RNA-1273)against COVID-19[EB/OL].(2020-06-11)[2020-07-09]. https：//investors.modernatx.com/newsreleases/news-release-details/moderna-advances-late-stagedevelopment-its-vaccine-mrna-1273.
• [25] GBN. Moderna-m RNA-1273[EB/OL].(2020-05-18)[2020-05-20]. https：//www.genengnews.com/covid-19-candidates/moderna/.
• [26] TU Y F,CHIEN C S,YARMISHYN A A,et al. A review of SARS-CoV-2 and the ongoing clinical trials[J]. Int J Mol Sci,2020,21(7). doi:10.3390/ijms21072657.
• [27] SMITH T R F,PATEL A,RAMOS S,et al. Immunogenicity of a DNA vaccine candidate for COVID-19[J]. Nat Communi,2020,11(1):2601.
• [28] LAM T T Y,SHUM M H H,ZHU H C,et al. Identifying SARS-CoV-2 related coronaviruses in Malayan pangolins[J].Nature,2020,583(7815):282-285.
• [29] CODAGENIX I. Codagenix announces the synthesis and preliminary safety of scalable,live-attenuated vaccine candidate against COVID-19[EB/OL].(2020-06-18)[2020-07-09]. https：//www.prnewswire.com/news-releases/codagenix-announces-thesynthesis-and-preliminary-safety-of-scalable-live-attenuatedvaccine-candidate-against-covid-19-301079306.html.
• [30] ZHENG M,WANG P,SONG W,et al. An A14U substitution in the 3'noncoding region of the M segment of viral RNA supports replication of influenza virus with an NS1 deletion by modulating alternative splicing of M segment mRNAs[J]. J Virol,2015,89(20):10273-10285.
• [31] KONG T U O H. HKU joins global partnership to develop COVID-19 vaccine[EB/OL].(2020-03-18)[2020-03-20]. https：//fightcovid19.hku.hk/hku-state-key-laboratory-for-emerging-infectious-diseases-joins-global-effort-to-develop-covid-19-vaccine/.
• [32] GBN. The University of Hong Kong(HKU)[EB/OL].(2020-05-18)[2020-05-20]. https：//www.genengnews.com/covid-19-candidates/the-university-of-hong-kong-hku/.
• [33] HE Y,RAPPUOLI R,DE GROOT A S,et al. Emerging vaccine informatics[J]. BioMed Res Int,2010,2010:218590.doi:10.1155/2010/218590.
• [34] DALSASS M,BROZZI A,MEDINI D,et al. Comparison of open-source reverse vaccinology programs for bacterial vaccine antigen discovery[J]. Frontiers Immunol,2019,10:113. doi:10.3389/fimmu.2019.00113.
• [35] ONG E,WONG M U,HUFFMAN A,et al. COVID-19 coronavirus vaccine design using reverse vaccinology and machine learning[J]. Frontiers Immunol,2020,11:1581. doi:10.3389/fimmu.2020.01581.
• [36] SAXENA S K. Coronavirus d isease 2019(COVID-19)[M]. Lucknow:Centre for Advanced Research,King George's Medical University,2020.
• [37] WANG S F,TSENG S P,YEN C H,et al. Antibody-dependent SARS coronavirus infection is mediated by antibodies against spike proteins[J]. Biochem Biophys Res Communi,2014,451(2):208-214.
• [38] YIP M S,LEUNG N H L,CHEUNG C Y,et al. Antibody-dependent infection of human macrophages by severe acute respiratory syndrome coronavirus[J]. Virol J,2014,11(1):82.
• [39] JAUME M,YIP M S,KAM Y W,et al. SARS CoV subunit vaccine:antibody-mediated neutralisation and enhancement[J].Hong Kong Med J,2012,18(Suppl 2):31-36.
• [40] SHMELKOV E,NADAS A,CARDOZO T. Could vaccination with AIDSVAX immunogens have resulted in antibody-dependent enhancement of HIV infection in human subjects[J]. Hum Vaccin&Immunother,2014,10(10):3013-3016.
• [41] KUZMINA N A,YOUNAN P,GILCHUK P,et al. Antibodydependent enhancement of Ebola virus infection by human antibodies isolated from survivors[J]. Cell Rep,2018,24(7):1802.
• [42] YANG Z,KONG W,HUANG Y,et al. A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice[J]. Nature,2004,428(6982):561-564.
• [43] SCHLAKE T,THESS A,FOTINMLECZEK M,et al. Developing mRNA-vaccine technologies[J]. RNA Biol, 2012, 9(11):1319-1330.
• [44] KORBER B,FISCHER W,GNANAKARAN S,et al. Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2[J]. bioRxiv,2020,2020.04.29.069054.doi:10.1101/2020.04.29.069054.
• [45] FERGUSON N,LAYDON D,NEDJATI GILANI G,et al.Report 9:Impact of non-pharmaceutical interventions(NPIs)to reduce COVID19 mortality and healthcare demand[EB/OL].(2020-03-16)[2020-03-20]. http：//hdl.handle.net/10044/1/77482.