新型冠状病毒疫苗的种类、机制及临床试验效果

林剑生 , 沈佳莹 , 曹广文

引用本文: 林剑生, 沈佳莹, 曹广文. 新型冠状病毒疫苗的种类、机制及临床试验效果[J]. 上海预防医学, 2021, 33(11): 1088-1095. doi: 10.19428/j.cnki.sjpm.2021.20991 shu
Citation: LIN Jian-sheng, SHEN Jia-ying, CAO Guang-wen . Category and working mechanisms of SARS-CoV-2 vaccines and their effectiveness in clinical trials[J]. Shanghai Journal of Preventive Medicine, 2021, 33(11): 1088-1095. doi: 10.19428/j.cnki.sjpm.2021.20991 shu

新型冠状病毒疫苗的种类、机制及临床试验效果

    作者简介: 林剑生,男,硕士在读;研究方向:公共卫生;E-mail:z549460739@163.com
    通讯作者: 曹广文, gcao@smmu.edu.cn
  • 基金项目: 国家自然科学基金(82041022);上海科学技术委员会项目(20JC1410200;20431900404)

摘要 : 自新型冠状病毒肺炎(COVID⁃19)暴发以来,全球累计确诊病例已超过120 915 219例,确诊死亡2 674 078例,超过223个国家或地区的经济和卫生资源遭受到不同程度的影响。目前,临床上尚无针对COVID⁃19的特效药,公共卫生政策实施难度大,各种疫苗的研发进展就引起了极大的关注。本文介绍了目前针对COVID⁃19开发较为热门的灭活疫苗、减毒活疫苗、重组亚单位疫苗、重组病毒载体疫苗、脱氧核糖核酸(DNA)疫苗和核糖核酸(RNA)疫苗的研究进展、优势和不足,提倡多个平台的疫苗共同研发,有助于更好地控制和预防COVID⁃19。

English

    1. [1]

      World Health Organization. WHO coronavirus(COVID-19)dashboard[EB/OL].(2021-03-18)[ 2021-03-18]. https://covid19.who.int.

    2. [2]

      YADDANAPUDI K, MENG S H, WHITT A G.Exosomes from GM-CSF expressing embryonic stem cells are an effective prophylactic vaccine for cancer prevention[J]. Oncoimmunology, 2019, 8, (3): 1561119-.

    3. [3]

      LIAO, WANG, KO Y A.Chimeric hemagglutinin vaccine elicits broadly protective CD4 and CD8 T cell responses against multiple influenza strains and subtypes[J]. Proc Natl Acad Sci USA, 2020, 117, (30): 17757-17763.

    4. [4]

      BLACK S, BLOOM D E, KASLOW D C.Transforming vaccine development[J]. Semin Immunol, 2020, 50: 101413-.

    5. [5]

      曹广文. 新型冠状病毒进化、相关流行特征和特异性防控中的关键问题[J]. 上海预防医学,2020,32(9):697- 703.

    6. [6]

      KETEMA D B, ASSEMIE M A, ALAMNEH A A.Full vaccination coverage among children aged 12~23 months in Ethiopia: a systematic review and meta-analysis[J]. BMC Public Health, 2020, 20, (1): 777-.

    7. [7]

      SOLEIMANPOUR S, YAGHOUBI A.COVID-19 vaccine: where are we now and where should we go?[J]. Expert Rev Vaccines, 2021, 20, (1): 23-44.

    8. [8]

      KRAMMER F.SARS-CoV-2 vaccines in development[J]. Nature, 2020, 586, (7830): 516-527.

    9. [9]

      LIU M A.Immunologic basis of vaccine vectors[J]. Immunity, 2010, 33, (4): 504-515.

    10. [10]

      ZHANG Y N, CHEN C, DENG C L.A novel rabies vaccine based on infectious propagating particles derived from hybrid VEEV-Rabies replicon[J]. EBioMedicine, 2020, 56: 102819-.

    11. [11]

      SCHILLER J T, LOWY D R.Raising expectations for subunit vaccine[J]. J Infect Dis, 2015, 211, (9): 1373-1375.

    12. [12]

      成传刚,慕婷,袁军,等. 重组病毒载体疫苗研究进展[J]. 中国病毒病杂志,2018,8(4):318- 328.

    13. [13]

      ZHANG S J, HUANG W X, ZHOU X Y.Seroprevalence of neutralizing antibodies to human adenoviruses type-5 and type-26 and chimpanzee adenovirus type-68 in healthy Chinese adults[J]. J Med Virol, 2013, 85, (6): 1077-1084.

    14. [14]

      WEKEN HVAN DER, COX E, DEVRIENDT B.Advances in oral subunit vaccine design[J]. Vaccines (Basel), 2020, 9, (1): 1-.

    15. [15]

      ARASHKIA A, JALILVAND S, MOHAJEL N.Severe acute respiratory syndrome-coronavirus-2 spike (S) protein based vaccine candidates: state of the art and future prospects[J]. Rev Med Virol, 2021, 31, (3): -.

    16. [16]

      WANG Z, TROILO P J, WANG X.Detection of integration of plasmid DNA into host genomic DNA following intramuscular injection and electroporation[J]. Gene Ther, 2004, 11, (8): 711-721.

    17. [17]

      KIM J, EYGERIS Y, GUPTA M.Self-assembled mRNA vaccines[J]. Adv Drug Deliv Rev, 2021, 170: 83-112.

    18. [18]

      TOMBÁCZ I, WEISSMAN D, PARDI N.Vaccination with messenger RNA: a promising alternative to DNA vaccination[J]. Methods Mol Biol, 2021, 2197: 13-31.

    19. [19]

      World Health Organization. COVID-19 vaccine tracker and landscape[EB/OL].(2021-03-02)[ 2021-03-18]. https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines.

    20. [20]

      XIA S L, ZHANG Y T, WANG Y X.Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trial[J]. Lancet Infect Dis, 2021, 21, (1): 39-51.

    21. [21]

      U.S. National Library of Medicine. Clinical trial to evaluate the efficacy,immunogenicity and safety of the inactivated SARS-CoV-2 vaccine(COVID-19)[EB/OL].(2020-11-27)[ 2021-03-18]. https://ClinicalTrials.gov/show/NCT04560881.

    22. [22]

      ZHANG Y J, ZENG G, PAN H X.Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18~59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial[J]. Lancet Infect Dis, 2021, 21, (2): 181-192.

    23. [23]

      WU Z W, HU Y L, XU M.Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial[J]. Lancet Infect Dis, 2021, 21, (6): 803-812.

    24. [24]

      U.S. National Library of Medicine. Clinical trial for SARS-CoV-2 vaccine(COVID-19)[EB/OL].(2020-10-09).[ 2021-03-18]. https://ClinicalTrials.gov/show/NCT04582344.

    25. [25]

      WANG H, ZHANG Y T, HUANG B Y.Development of an inactivated vaccine candidate, BBIBP-CorV, with potent protection against SARS-CoV-2[J]. Cell, 2020, 182, (3): 713-721.

    26. [26]

      ELLA R, VADREVU K M, JOGDAND H.Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBV152: a double-blind, randomised, phase 1 trial[J]. Lancet Infect Dis, 2021, 21, (5): 637-646.

    27. [27]

      SU F, PATEL G B, HU S H.Induction of mucosal immunity through systemic immunization: phantom or reality?[J]. Hum Vaccin Immunother, 2016, 12, (4): 1070-1079.

    28. [28]

      MANGTANI P, ABUBAKAR I, ARITI C.Protection by BCG vaccine against tuberculosis: a systematic review of randomized controlled trials[J]. Clin Infect Dis, 2014, 58, (4): 470-480.

    29. [29]

      v-vi .Systematic review and meta-analysis of the current evidence on the duration of protection by bacillus Calmette-Guérin vaccination against tuberculosis[J]. Health Technol Assess, 2013, 17, (37): 1-372.

    30. [30]

      O’NEILL L A J, NETEA M G.BCG-induced trained immunity: can it offer protection against COVID-19?[J]. Nat Rev Immunol, 2020, 20, (6): 335-337.

    31. [31]

      SHARMA A, SHARMA S K, SHI Y F.BCG vaccination policy and preventive chloroquine usage: do they have an impact on COVID-19 pandemic?[J]. Cell Death Dis, 2020, 11, (7): 516-.

    32. [32]

      ESCOBAR L E, MOLINA-CRUZ A, BARILLAS-MURY C.BCG vaccine protection from severe coronavirus disease 2019 (COVID-19)[J]. Proc Natl Acad Sci USA, 2020, 117, (30): 17720-17726.

    33. [33]

      CHIMOYI L, VELEN K, CHURCHYARD G J.An ecological study to evaluate the association of Bacillus Calmette-Guerin (BCG) vaccination on cases of SARS-CoV2 infection and mortality from COVID-19[J]. PLoS One, 2020, 15, (12): -.

    34. [34]

      LIU S J, YUAN C H, LIN J F.Association between vaccinations and clinical manifestations in children with COVID-19[J]. Transl Pediatr, 2021, 10, (1): 17-25.

    35. [35]

      U.S. National Library of Medicine. A phase Ⅲ clinical trial to determine the safety and efficacy of ZF2001 for prevention of COVID-19[EB/OL].(2020-11-30)[ 2021-03-18]. https://ClinicalTrials.gov/show/NCT04646590.

    36. [36]

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

    37. [37]

      YANG S L, LI Y, DAI L P.Safety and immunogenicity of a recombinant tandem-repeat dimeric RBD protein vaccine against COVID-19 in adults: pooled analysis of two randomized, double-blind, placebo-controlled, phase 1 and 2 trials[J]. medRxiv, 2020, : -. doi: 10.1101/2020.12.20.20248602

    38. [38]

      U.S. National Library of Medicine. A study to evaluate the efficacy,responseimmune,and safety of a COVID-19 vaccine in adults ≥18 years with a pediatric expansion in adolescents(12 to< 18 years)at risk for SARS-CoV-2[EB/OL].(2020-11-02).[ 2021-03-18]. https://ClinicalTrials.gov/show/NCT04611802.

    39. [39]

      U.S. National Library of Medicine. A controlled phase 2/ 3 study of adjuvanted recombinant SARS-CoV-2 trimeric S-protein vaccine(SCB-2019)for the prevention of COVID-19(SCB- 2019)[EB/OL].(2021-02-09).[ 2021-03-18]. https://ClinicalTrials.gov/show/NCT04672395.

    40. [40]

      KEECH C, ALBERT G, CHO I.Phase 1~2 trial of a SARS-CoV-2 recombinant spike protein nanoparticle vaccine[J]. N Engl J Med, 2020, 383, (24): 2320-2332.

    41. [41]

      RICHMOND P, HATCHUEL L, DONG M.Safety and immunogenicity of S-Trimer (SCB-2019), a protein subunit vaccine candidate for COVID-19 in healthy adults: a phase 1, randomised, double-blind, placebo-controlled trial[J]. Lancet, 2021, 397, (10275): 682-694.

    42. [42]

      ZHU F C, LI Y H, GUAN X H.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, 2020, 395, (10240): 1845-1854.

    43. [43]

      U.S. National Library of Medicine. Phase Ⅲ trial of A COVID-19 vaccine of adenovirus vector in adults 18 years old and above[EB/OL].(2021-01-22).[ 2021-03-18]. https://ClinicalTrials.gov/show/NCT04526990.

    44. [44]

      RAMASAMY M N, MINASSIAN A M, EWER K J.Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial[J]. Lancet, 2021, 396, (10267): 1979-1993.

    45. [45]

      ZHU F C, GUAN X H, LI Y H.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, placebo-controlled, phase 2 trial[J]. Lancet, 2020, 396, (10249): 479-488.

    46. [46]

      FOLEGATTI P M, EWER K J, ALEY P K.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.

    47. [47]

      SADOFF J, LE GARS M, SHUKAREV G.Interim results of a phase 1-2a trial of Ad26.COV2.S covid-19 vaccine[J]. N Engl J Med, 2021, 384, (19): 1824-1835.

    48. [48]

      LOGUNOV D Y, DOLZHIKOVA I V, SHCHEBLYAKOV D V.Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomised controlled phase 3 trial in Russia[J]. Lancet, 2021, 397, (10275): 671-681.

    49. [49]

      U.S. National Library of Medicine. A study to assess safety,tolerability,and ofVimmunogenicity591(COVID-19 vaccine)in healthy participants(V591- 001)[EB/OL].(2021-03-11)[ 2021-03-18]. https://ClinicalTrials.gov/show/NCT04498247.

    50. [50]

      U.S. National Library of Medicine. Safety and immunogenicity of the candidate vaccine MVA-SARS-2-S and a booster vaccination with a licensed vaccine against COVID-19[EB/OL].(2020-09-29)[ 2021-03-18]. https://ClinicalTrials.gov/show/NCT04569383.

    51. [51]

      U.S. National Library of Medicine. Phase Ⅰ~Ⅱ trial of dendritic cell vaccine to prevent COVID-19 in adults[EB/OL].(2020-05-13)[ 2021-03-18]. https://ClinicalTrials.gov/show/NCT04386252.

    52. [52]

      U.S. National Library of Medicine. Immunity and safety of Covid-19 synthetic minigene vaccine[EB/OL].(2020-03-19)[ 2021-03-18]. https://ClinicalTrials.gov/show/NCT04276896.

    53. [53]

      TEBAS P, YANG S P, BOYER J D.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, 2021, 31: 100689-.

    54. [54]

      U.S. National Library of Medicine. Safety,immunogenicity,and efficacy of INO-4800 for COVID-19 in healthy seronegative adults at high risk of SARS-CoV-2 exposure[EB/OL].(2020-11-24)[ 2021-03-18]. https://ClinicalTrials.gov/show/NCT04642638.

    55. [55]

      WALSH E E, FRENCK R W JR, FALSEY A R.Safety and immunogenicity of two RNA-based COVID-19 vaccine candidates[J]. N Engl J Med, 2020, 383, (25): 2439-2450.

    56. [56]

      MULLIGAN M J, LYKE K E, KITCHIN N.Phase Ⅰ/Ⅱ study of COVID-19 RNA vaccine BNT162b1 in adults[J]. Nature, 2020, 586, (7830): 589-593.

    57. [57]

      POLACK F P, THOMAS S J, KITCHIN N.Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine[J]. N Engl J Med, 2020, 383, (27): 2603-2615.

    58. [58]

      BADEN L R, SAHLY H MEL, ESSINK B.Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine[J]. N Engl J Med, 2021, 384, (5): 403-416.

    59. [59]

      DOLGIN E.COVID-19 vaccines poised for launch, but impact on pandemic unclear[J]. Nat Biotechnol, 2020, : -. doi: 10.1038/d41587-020-00022-y

    60. [60]

      CANDIDO D S, CLARO I M, DE JESUS J G.Evolution and epidemic spread of SARS-CoV-2 in Brazil[J]. Science, 2020, 369, (6508): 1255-1260.

    61. [61]

      MUNNINK B B O, SIKKEMA R S, NIEUWENHUIJSE D F.Transmission of SARS-CoV-2 on mink farms between humans and mink and back to humans[J]. Science, 2021, 371, (6525): 172-177.

    62. [62]

      LIU Y, LIU J Y, XIA H J.Neutralizing activity of BNT162b2-elicited serum-preliminary report[J]. N Engl J Med, 2021, 384: 1466-1468.

    63. [63]

      SAHIN U, MUIK A, DERHOVANESSIAN E.COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses[J]. Nature, 2020, 586, (7830): 594-599.

    64. [64]

      YANG P H, DING Y B, XU Z.Increased circulating level of interleukin-6 and CD8+ T cell exhaustion are associated with progression of COVID-19[J]. Infect Dis Poverty, 2020, 9, (1): 161-.

    65. [65]

      JACKSON L A, ANDERSON E J, ROUPHAEL N G.An mRNA vaccine against SARS-CoV-2 preliminary report[J]. N Engl J Med, 2020, 383, (20): 1920-1931.

    66. [66]

      徐芳,刘爽,严非,等. 国际疫苗监测系统管理经验借鉴[J]. 上海预防医学,2021,33(1):73- 78.

    1. [1]

      王霖 , 杜映荣 , 马志强 , 李杰 , 张淑琼 , 汤晓青 , 瞿春燕 , 段亚茹 , 李才信 . 新型冠状病毒疫苗接种6个月后血清IgMIgG抗体水平的分析. 上海预防医学, 2022, 34(2): 126-129. doi: 10.19428/j.cnki.sjpm.2022.21598

    2. [2]

      崔军 , 张涛 , 李辉 , 史碧君 . 社区慢性阻塞性肺疾病患者流感和肺炎疫苗接种意愿及影响因素. 上海预防医学, 2015, 27(7): 411-413.

    3. [3]

      刘赛朵 , 蒋贤高 , 宁洪叶 , 叶新春 , 潘宁 , 吴正兴 , 周月影 , 邱超超 , 施伎蝉 . 42例新型冠状病毒肺炎的临床特征分析. 上海预防医学, 2020, 32(9): 736-739. doi: 10.19428/j.cnki.sjpm.2020.20092

    4. [4]

      朱竹先 , 张晓林 , 李旭 , 张子强 . 高龄新型冠状病毒肺炎患者肝肾及凝血功能损伤的临床特征分析. 上海预防医学, 2020, 32(9): 732-735,745. doi: 10.19428/j.cnki.sjpm.2020.20345

    5. [5]

      李环 , 徐健峰 , 孙晓丽 , 姚启哲 , 郭微 , 齐红霞 , 孙畅 . 辽宁省盘锦市12例新型冠状病毒肺炎的临床转归分析. 上海预防医学, 2020, 32(11): 918-921. doi: 10.19428/j.cnki.sjpm.2020.20355

    6. [6]

      刘捷宸 , 陈勇 , 孙晓冬 , 沈妍琼 , 刘念 , 朱芳军 . 电子签名技术在疫苗冷链温度监测管理中的应用. 上海预防医学, 2020, 32(8): 614-617. doi: 10.19428/j.cnki.sjpm.2020.19871

    7. [7]

      邓子如 , 严非 , 王伟 , 阿克忠 , 付朝伟 . 国际组织关于疫苗冷链配送的管理与实践及启示. 上海预防医学, 2021, 33(2): 141-145, 162. doi: 10.19428/j.cnki.sjpm.2021.20146

    8. [8]

      臧召燕 , 王伟 , 严非 , 阿克忠 , 付朝伟 . 中国和亚洲部分其他国家疫苗配送管理的比较分析. 上海预防医学, 2021, 33(3): 243-247,253. doi: 10.19428/j.cnki.sjpm.2021.20145

    9. [9]

      李保军 , 平建明 , 林鸿波 , 孙烨祥 . 手足口病疫苗接种年龄区间的流行病学探讨. 上海预防医学, 2014, 26(1): 10-13.

    10. [10]

      刘敏勇 , 黄卓英 , 陆箐 , 杨建萍 , 杨玉颖 . 2015-2016年上海市脊髓灰质炎疫苗免疫策略调整前后婴儿抗体水平变化. 上海预防医学, 2020, 32(8): 627-630. doi: 10.19428/j.cnki.sjpm.2020.18789

    11. [11]

      徐芳 , 刘爽 , 严非 , 王伟 , 阿克忠 , 付朝伟 . 国际疫苗监测系统管理经验借鉴. 上海预防医学, 2021, 33(1): 73-78. doi: 10.19428/j.cnki.sjpm.2021.20144

    12. [12]

      孙晓冬 . 规范预防接种工作, 加强疫苗安全性评价. 上海预防医学, 2019, 31(4): 249-250. doi: 10.19428/j.cnki.sjpm.2019.19429

    13. [13]

      朱珠英 , 郑琼琼 . 温州市龙湾区扩大国家免疫规划疫苗接种率调查. 上海预防医学, 2019, 31(7): 568-573. doi: 10.19428/j.cnki.sjpm.2019.18678

    14. [14]

      陈一凡 , 曹广文 . 全国新型冠状病毒肺炎发病趋势初步分析. 上海预防医学, 2020, 32(2): 147-150. doi: 10.19428/j.cnki.sjpm.2020.20053

    15. [15]

      王英鉴 , 张娜 , 吕涵路 , 周艺彪 . 上海市新型冠状病毒肺炎发病趋势初步分析. 上海预防医学, 2020, 32(2): 142-146. doi: 10.19428/j.cnki.sjpm.2020.20041

    16. [16]

      韩明慧 , 方虹霁 , 杨东见 , 姜晨彦 , 陈传炜 , 王和兴 . 国外新型冠状病毒肺炎发病的现状和趋势分析. 上海预防医学, 2020, 32(3): 211-215. doi: 10.19428/j.cnki.sjpm.2020.20063

    17. [17]

      王继伟 , 谷本哲也 , 赵天辰 , 津田健司 , 山下Erika , 上昌广 , 姜庆五 . 日本新型冠状病毒肺炎传播初期阶段的流行现状及应对. 上海预防医学, 2020, 32(4): 314-319. doi: 10.19428/j.cnki.sjpm.2020.20107

    18. [18]

      谭晓㛃 , 钱治军 , 张宏伟 . 全国新型冠状病毒肺炎疫情初期治愈和死亡情况分析. 上海预防医学, 2020, 32(4): 309-313. doi: 10.19428/j.cnki.sjpm.2020.20081

    19. [19]

      李文豪 , 熊鹏 , 赵心海 , 陈衍芳 , 刘博 , 刘敏 , 陈青山 . 中国应对新型冠状病毒肺炎本土疫情的策略和经验. 上海预防医学, 2020, 32(9): 704-711. doi: 10.19428/j.cnki.sjpm.2020.20326

    20. [20]

      甄玲燕 , 应圣洁 , 吴蕴华 , 赵琬 , 朱效宁 , 丁克颖 . 新型冠状病毒肺炎防控留观酒店空调卫生状况调查. 上海预防医学, 2021, 33(6): 496-499. doi: 10.19428/j.cnki.sjpm.2021.20436

  • 加载中
计量
  • PDF下载量: 65
  • 文章访问数: 1408
  • 引证文献数: 0
文章相关
  • 通讯作者: 曹广文, gcao@smmu.edu.cn
  • 收稿日期: 2021-03-19
  • 网络出版日期: 2021-11-20
通讯作者: 陈斌, bchen63@163.com
  • 1. 

    沈阳化工大学材料科学与工程学院 沈阳 110142

  1. 本站搜索
  2. 百度学术搜索
  3. 万方数据库搜索
  4. CNKI搜索

/

返回文章