2021 01 v.30 64-72
新型冠状病毒疫苗研发进展及其潜在不良反应
基金项目(Foundation):
2019年上海市临床重点专科项目-临床药学专业（编号shslczdzk06502）
邮箱(Email):
hs@126.com;
DOI:
10.19577/j.1007-4406.2021.01.017
中文作者单位:
复旦大学附属华山医院药剂科;
摘要(Abstract):
新型冠状病毒感染是目前危害全球的传染性疾病,造成约1亿人感染和200万人死亡。在缺乏有效抗病毒药物的情况下,疫苗成为全球防控新冠病毒的重要方法,在我国已经有超过1 000万人注射了灭活疫苗。从疫苗的研发机制、研发进展和潜在的不良反应3个方面,系统综述新型冠状病毒的灭活疫苗、减毒疫苗、亚单位疫苗、RNA疫苗、DNA疫苗和病毒载体疫苗,供医药专业人员开展新型冠状病毒疫苗临床安全性监察和社会公众科普学习。
关键词(KeyWords):
疫苗;新型冠状病毒;不良反应监测
| 4,278 | 24 | 42 |
| 下载次数 | 被引频次 | 阅读次数 |
参考文献
[1]WHO.Draft landscape of covid-19 candidate vaccines[EB/OL].(2021-01-08)[2021-01-12].https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines.
[2]康庄,唐梅.新型冠状病毒疫苗的研发进展及分析[J].生物医学工程学杂志,2020,37(3):373.
[3]白玉,李敏,高恩明.病毒灭活疫苗生产工艺要点[J].中国生物制品学杂志,2011,24(9):1116.
[4]黄腾,李艳萍,万宗举,等.甲肝灭活疫苗(Vero细胞)在2岁以上中国健康人群的免疫原性和安全性研究[J].应用预防医学,2016,22(3):193.
[5]白仲虎,李昕然,王荣斌,等.哺乳动物细胞生产人用灭活疫苗相关技术进展[J].中国细胞生物学学报,2019,41(10):1986.
[6]RAWAT K,KUMARI P,SAHA L.COVID-19 vaccine:a recent update in pipeline vaccines,their design and development strategies[J].Eur J Pharmacol,2020,892:173751.
[7]ZHU F C,GUAN X H,LI Y H,et al.Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older:a randomised,double-blind,placebocontrolled,phase 2 trial[J].Lancet,2020,396(10249):479.
[8]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,2020,324(10):951.
[9]JACKSON L A,ANDERSON E J,ROUPHAEL N G,et al An mRNA vaccine against SARS-COV-2:preliminary report[J].NEngl J Med,2020,383(12):1190.
[10]XIA S,ZHANG Y,WANG Y,et al.Safety and immunogenicity of an inactivated SARS-CoV-2,BBIBP-CorV:a randomised,doubleblind,placebo-controlled,phase 1/2 trial[J].Lancet Infect Dis,2021,21(1):39.
[11]刘昌孝,伊秀林,崔涛,等.新型冠状病毒疫苗研发与评价[J].药物评价研究,2020,43(7):1421.
[12]李征,刘晔,李春阳.减毒活疫苗的应用及其研究进展[J].中国生物制品学杂志,2018,31(2):205.
[13]宋全伟,王华庆.不同技术路线研发新型冠状病毒疫苗的特性和研究进展[J].中华医学杂志,2020,100(38):3030.
[14]SEO S H,JANG Y.Cold-adapted live attenuated SARSCoV-2 vaccine completely protects human ACE2 transgenic mice from SARS-CoV-2 infection[J].Vaccines,2020,8(4).DOI:10.1101/2020.08.04.235689.
[15]LAU S Y,WANG P,MOK B W Y,et al.Attenuated SARSCoV-2 variants with deletions at the S1/S2 junction[J].Emerg Microbes Infect,2020,9(1):837.
[16]TODOROV G,UVERSKY V N.A possible path towards rapid development of live-attenuated SARS-CoV-2 vaccines:plunging into the natural pool[J].Biomolecules,2020,10(10):1438.
[17]KAUR S P,GUPTA V.COVID-19 Vaccine:a comprehensive status report[J].Virus Res,2020,288:198114.
[18]JEYANATHAN M,AFKHAMI S,SMAILL F,et al.Immunological considerations for COVID-19 vaccine strategies[J].Nat Rev Immunol,2020,20(10):615.
[19]GRAHAM B S.Advances in antiviral vaccine development[J].Immunol Rev,2013,255(1):230.
[20]ANHUI ZHIFEILONGKOMA BIOPHARMACEUTICAL CO.L.A randomized,double-blind,placebo-controlled phase III clinical trial of the effectiveness and safety of inoculation of recombinant new coronavirus vaccine (CHO cells) in the prevention of COVID-19 in people 18 years and olderage[EB/OL].(2020-11-22)[2020-01-12].http://www.chictr.org.cn/showprojen.aspx?proj=64718
[21]KEECH C,ALBERT G,CHO I,et al.Phase 1-2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine[J].N Engl J Med,2020,383(24):2320.
[22]Novavax.Evaluation of the Safety and Immunogenicity of a SARSCoV-2 rS (COVID-19) Nanoparticle Vaccine With/Without Matrixm adjuvant[EB/OL].(2020-05-27)[2020-01-12].https://clinicaltrials.gov/ct2/show/NCT04368988?term=vaccine&recrs=a&cond=covid-19&draw=2.
[23]LI Y D,CHI W Y,SU J H,et al.Coronavirus vaccine development:from SARS and MERS to COVID-19[J].J Biomed Sci,2020,27(1):1.
[24]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 Commun,2014,451(2):208.
[25]TIAN J H,PATEL N,HAUPTR,et al.SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice[J].Nat Commun,2021,12(1):372.
[26]YI C,YI Y,LI J.mRNA vaccines:possible tools to combat SARSCoV-2[J].Virol Sin,2020,35(3):259.
[27]ABBASI J.COVID-19 and mRNA vaccines-first large test for a new approach[J].JAMA,2020,324(12):1125.
[28]葛华,蒋丽勇,刘术,等.COVID-19 mRNA疫苗关键技术与产品进展分析[J].军事医学,2020,44(4):264.
[29]ANDERSON E J,ROUPHAEL N G,WIDGE A T,et al.Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults[J].N Engl J Med,2020,383(25):2427.
[30]POLACK F P,THOMAS S J,KITCHIN N,et al.Safety and efficacy of the BNT162b2 mRNA covid-19 vaccine[J].N Engl JMed,2020,383(27):2603.
[31]张琳,李燕,安志杰.新型冠状病毒mRNA疫苗研发进展[J].中国疫苗和免疫,2020,26(3):349.
[32]LU D,BENJAMIN R,KIM M,et al.Optimization of methods to achieve mRNA-mediated transfection of tumor cells in vitro and in vivo employing cationic liposome vectors[J].Cancer Gene Ther,1994,1(4):245.
[33]CASTELLS M C,PHILLIPS E J.Maintaining safety with SARSCoV-2 vaccines[J].N Engl J Med,2020.DOI:10.1056/NEJMra2035343.
[34]STONE C A,LIU Y W,RELLING M V,et al.Immediate hypersensitivity to polyethylene glycols and polysorbates:more common than we have recognized[J].J Allergy Clin Immunol:Pract,2019,7(5):1533.
[35]SELLATURAY P,NASSER S,EWAN P.Polyethylene glycol-induced systemic allergic reactions (anaphylaxis)[J/OL].J Allergy Clin Immunol:Pract,2020.(2020-10-01)[2021-01-12].https://doi.org/10.1016/j.jaip.2020.09.029.
[36]SILVEIRA M M,OLIVEIRA T L,SCHUCH R A,et al.DNAvaccines against leptospirosis:a literature review[J].Vaccine,2017,35(42):5559.
[37]SILVEIRA M M,MOREIRA G M S G,MENDONM.DNAvaccines against COVID-19:Perspectives and challenges[J].Life Sci,2021,267(3):118919.
[38]YU J Y,TOSTANOSKI L H,PETER L,et al.DNA vaccine protection against SARS-CoV-2 in rhesus macaques[J].Science,2020,369(6505):806.
[39]TEBAS P,YANG S P,BOYER J D,et al.Safety and immunogenicity of INO-4800 DNA vaccine against SARS-CoV-2:a preliminary report of an open-label,Phase 1 clinical trial[J].EClinicalMedicine,2020:100689.
[40]WANG W,SAEED M,ZHOU Y,et al.Non-viral gene delivery for cancer immunotherapy[J].J Gene Med,2019,21(7):e3092.
[41]COBAN C,KOBIYAMA K,JOUNAI N,et al.DNA vaccines:a simple DNA sensing matter?[J].Hum Vaccin Immunother,2013,9(10):2216.
[42]WALLS A C,PARK Y J,TORTORICI M A,et al.Structure,function,and antigenicity of the SARS-CoV-2 spike glycoprotein[J].Cell,2020,181(2):281.
[43]HUMPHREYS I R,SEBASTIAN S.Novel viral vectors in infectious diseases[J].Immunology,2018,153(1):1.
[44]杨勇,周东明.腺病毒载体疫苗的临床研究进展[J].生命的化学,2014,34(1):46.
[45]HASSAN A O,KAFAI N M,DMITRIEV I P,et al.A single-dose intranasal ChAd vaccine protects upper and lower respiratory tracts against SARS-CoV-2[J].Cell,2020,183(1):169.
[46]CAPONE S D A A,AMMENDOLA V,COLLOCA S,et al.Development of chimpanzee adenoviruses as vaccine vectors[J].Expert Rev Vaccines,2013,12(4):379.
[47]VOYSEY M,CLEMENS S A C,MADHI S A,et al.Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2:an interim analysis of four randomised controlled trials in Brazil,South Africa,and the UK[J].Lancet,2021,397(10269):99.
[48]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.
[49]SADOFF J,GARS M L,SHUKAREV G,et al.Safety and immunogenicity of the Ad26.COV2.S COVID-19 vaccine candidate:interim results of a phase 1/2a,double-blind,randomized,placebo-controlled trial[EB/OL].2020.https://doi.org/10.1101/2020.09.23.20199604.
[50]ZHU F C,GUAN X H,LI Y H,et al.Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older:a randomised,doubleblind,placebo-controlled,phase 2 trial[J].Lancet,2020,396(10249):479.
[51]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,fi rst-in-human trial[J].Lancet,2020,395(10240):1845.
[52]LOGUNOV D Y,DOLZHIKOVA I V,ZUBKOVA O V,et al.Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations:two open,non-randomised phase 1/2 studies from Russia[J].Lancet,2020,396(10255):887.
[2]康庄,唐梅.新型冠状病毒疫苗的研发进展及分析[J].生物医学工程学杂志,2020,37(3):373.
[3]白玉,李敏,高恩明.病毒灭活疫苗生产工艺要点[J].中国生物制品学杂志,2011,24(9):1116.
[4]黄腾,李艳萍,万宗举,等.甲肝灭活疫苗(Vero细胞)在2岁以上中国健康人群的免疫原性和安全性研究[J].应用预防医学,2016,22(3):193.
[5]白仲虎,李昕然,王荣斌,等.哺乳动物细胞生产人用灭活疫苗相关技术进展[J].中国细胞生物学学报,2019,41(10):1986.
[6]RAWAT K,KUMARI P,SAHA L.COVID-19 vaccine:a recent update in pipeline vaccines,their design and development strategies[J].Eur J Pharmacol,2020,892:173751.
[7]ZHU F C,GUAN X H,LI Y H,et al.Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older:a randomised,double-blind,placebocontrolled,phase 2 trial[J].Lancet,2020,396(10249):479.
[8]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,2020,324(10):951.
[9]JACKSON L A,ANDERSON E J,ROUPHAEL N G,et al An mRNA vaccine against SARS-COV-2:preliminary report[J].NEngl J Med,2020,383(12):1190.
[10]XIA S,ZHANG Y,WANG Y,et al.Safety and immunogenicity of an inactivated SARS-CoV-2,BBIBP-CorV:a randomised,doubleblind,placebo-controlled,phase 1/2 trial[J].Lancet Infect Dis,2021,21(1):39.
[11]刘昌孝,伊秀林,崔涛,等.新型冠状病毒疫苗研发与评价[J].药物评价研究,2020,43(7):1421.
[12]李征,刘晔,李春阳.减毒活疫苗的应用及其研究进展[J].中国生物制品学杂志,2018,31(2):205.
[13]宋全伟,王华庆.不同技术路线研发新型冠状病毒疫苗的特性和研究进展[J].中华医学杂志,2020,100(38):3030.
[14]SEO S H,JANG Y.Cold-adapted live attenuated SARSCoV-2 vaccine completely protects human ACE2 transgenic mice from SARS-CoV-2 infection[J].Vaccines,2020,8(4).DOI:10.1101/2020.08.04.235689.
[15]LAU S Y,WANG P,MOK B W Y,et al.Attenuated SARSCoV-2 variants with deletions at the S1/S2 junction[J].Emerg Microbes Infect,2020,9(1):837.
[16]TODOROV G,UVERSKY V N.A possible path towards rapid development of live-attenuated SARS-CoV-2 vaccines:plunging into the natural pool[J].Biomolecules,2020,10(10):1438.
[17]KAUR S P,GUPTA V.COVID-19 Vaccine:a comprehensive status report[J].Virus Res,2020,288:198114.
[18]JEYANATHAN M,AFKHAMI S,SMAILL F,et al.Immunological considerations for COVID-19 vaccine strategies[J].Nat Rev Immunol,2020,20(10):615.
[19]GRAHAM B S.Advances in antiviral vaccine development[J].Immunol Rev,2013,255(1):230.
[20]ANHUI ZHIFEILONGKOMA BIOPHARMACEUTICAL CO.L.A randomized,double-blind,placebo-controlled phase III clinical trial of the effectiveness and safety of inoculation of recombinant new coronavirus vaccine (CHO cells) in the prevention of COVID-19 in people 18 years and olderage[EB/OL].(2020-11-22)[2020-01-12].http://www.chictr.org.cn/showprojen.aspx?proj=64718
[21]KEECH C,ALBERT G,CHO I,et al.Phase 1-2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine[J].N Engl J Med,2020,383(24):2320.
[22]Novavax.Evaluation of the Safety and Immunogenicity of a SARSCoV-2 rS (COVID-19) Nanoparticle Vaccine With/Without Matrixm adjuvant[EB/OL].(2020-05-27)[2020-01-12].https://clinicaltrials.gov/ct2/show/NCT04368988?term=vaccine&recrs=a&cond=covid-19&draw=2.
[23]LI Y D,CHI W Y,SU J H,et al.Coronavirus vaccine development:from SARS and MERS to COVID-19[J].J Biomed Sci,2020,27(1):1.
[24]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 Commun,2014,451(2):208.
[25]TIAN J H,PATEL N,HAUPTR,et al.SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 immunogenicity in baboons and protection in mice[J].Nat Commun,2021,12(1):372.
[26]YI C,YI Y,LI J.mRNA vaccines:possible tools to combat SARSCoV-2[J].Virol Sin,2020,35(3):259.
[27]ABBASI J.COVID-19 and mRNA vaccines-first large test for a new approach[J].JAMA,2020,324(12):1125.
[28]葛华,蒋丽勇,刘术,等.COVID-19 mRNA疫苗关键技术与产品进展分析[J].军事医学,2020,44(4):264.
[29]ANDERSON E J,ROUPHAEL N G,WIDGE A T,et al.Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults[J].N Engl J Med,2020,383(25):2427.
[30]POLACK F P,THOMAS S J,KITCHIN N,et al.Safety and efficacy of the BNT162b2 mRNA covid-19 vaccine[J].N Engl JMed,2020,383(27):2603.
[31]张琳,李燕,安志杰.新型冠状病毒mRNA疫苗研发进展[J].中国疫苗和免疫,2020,26(3):349.
[32]LU D,BENJAMIN R,KIM M,et al.Optimization of methods to achieve mRNA-mediated transfection of tumor cells in vitro and in vivo employing cationic liposome vectors[J].Cancer Gene Ther,1994,1(4):245.
[33]CASTELLS M C,PHILLIPS E J.Maintaining safety with SARSCoV-2 vaccines[J].N Engl J Med,2020.DOI:10.1056/NEJMra2035343.
[34]STONE C A,LIU Y W,RELLING M V,et al.Immediate hypersensitivity to polyethylene glycols and polysorbates:more common than we have recognized[J].J Allergy Clin Immunol:Pract,2019,7(5):1533.
[35]SELLATURAY P,NASSER S,EWAN P.Polyethylene glycol-induced systemic allergic reactions (anaphylaxis)[J/OL].J Allergy Clin Immunol:Pract,2020.(2020-10-01)[2021-01-12].https://doi.org/10.1016/j.jaip.2020.09.029.
[36]SILVEIRA M M,OLIVEIRA T L,SCHUCH R A,et al.DNAvaccines against leptospirosis:a literature review[J].Vaccine,2017,35(42):5559.
[37]SILVEIRA M M,MOREIRA G M S G,MENDONM.DNAvaccines against COVID-19:Perspectives and challenges[J].Life Sci,2021,267(3):118919.
[38]YU J Y,TOSTANOSKI L H,PETER L,et al.DNA vaccine protection against SARS-CoV-2 in rhesus macaques[J].Science,2020,369(6505):806.
[39]TEBAS P,YANG S P,BOYER J D,et al.Safety and immunogenicity of INO-4800 DNA vaccine against SARS-CoV-2:a preliminary report of an open-label,Phase 1 clinical trial[J].EClinicalMedicine,2020:100689.
[40]WANG W,SAEED M,ZHOU Y,et al.Non-viral gene delivery for cancer immunotherapy[J].J Gene Med,2019,21(7):e3092.
[41]COBAN C,KOBIYAMA K,JOUNAI N,et al.DNA vaccines:a simple DNA sensing matter?[J].Hum Vaccin Immunother,2013,9(10):2216.
[42]WALLS A C,PARK Y J,TORTORICI M A,et al.Structure,function,and antigenicity of the SARS-CoV-2 spike glycoprotein[J].Cell,2020,181(2):281.
[43]HUMPHREYS I R,SEBASTIAN S.Novel viral vectors in infectious diseases[J].Immunology,2018,153(1):1.
[44]杨勇,周东明.腺病毒载体疫苗的临床研究进展[J].生命的化学,2014,34(1):46.
[45]HASSAN A O,KAFAI N M,DMITRIEV I P,et al.A single-dose intranasal ChAd vaccine protects upper and lower respiratory tracts against SARS-CoV-2[J].Cell,2020,183(1):169.
[46]CAPONE S D A A,AMMENDOLA V,COLLOCA S,et al.Development of chimpanzee adenoviruses as vaccine vectors[J].Expert Rev Vaccines,2013,12(4):379.
[47]VOYSEY M,CLEMENS S A C,MADHI S A,et al.Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2:an interim analysis of four randomised controlled trials in Brazil,South Africa,and the UK[J].Lancet,2021,397(10269):99.
[48]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.
[49]SADOFF J,GARS M L,SHUKAREV G,et al.Safety and immunogenicity of the Ad26.COV2.S COVID-19 vaccine candidate:interim results of a phase 1/2a,double-blind,randomized,placebo-controlled trial[EB/OL].2020.https://doi.org/10.1101/2020.09.23.20199604.
[50]ZHU F C,GUAN X H,LI Y H,et al.Immunogenicity and safety of a recombinant adenovirus type-5-vectored COVID-19 vaccine in healthy adults aged 18 years or older:a randomised,doubleblind,placebo-controlled,phase 2 trial[J].Lancet,2020,396(10249):479.
[51]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,fi rst-in-human trial[J].Lancet,2020,395(10240):1845.
[52]LOGUNOV D Y,DOLZHIKOVA I V,ZUBKOVA O V,et al.Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations:two open,non-randomised phase 1/2 studies from Russia[J].Lancet,2020,396(10255):887.
基本信息:
DOI：10.19577/j.1007-4406.2021.01.017
中图分类号:R392-3
引用信息:
[1]邱晓燕,杨慧莹,颜明明等.新型冠状病毒疫苗研发进展及其潜在不良反应[J].中国临床药学杂志,2021,30(01):64-72.DOI:10.19577/j.1007-4406.2021.01.017.
基金信息:
2019年上海市临床重点专科项目-临床药学专业（编号shslczdzk06502）