- 1. College of Life Science, Leshan Normal University, Leshan, Sichuan 614000, P.R.China;
- 2. Department of Biotechnology, Chengdu Institute of Biological Products, Chengdu 610000, P.R.China;
As the COVID-19 pandemic is intensifying globally, more and more people are pinning their hopes on the development of vaccines. At present, there are many research teams who have adopted different vaccine technology routes to develop 2019-nCoV vaccines. This article reviews and analyzes the current development and research status of 2019-nCoV vaccines in different routes, and explores their possible development in the future.
Citation： KANG Zhuang, TANG mei. Progress and analysis on the development of 2019-nCoV vaccine. Journal of Biomedical Engineering, 2020, 37(3): 373-379. doi: 10.7507/1001-5515.202004025 Copy
Copyright ? the editorial department of Journal of Biomedical Engineering of West China Medical Publisher. All rights reserved
| 1. | Chen Nanshan, Zhou Min, Dong Xuan, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet, 2020, 395(1223): 507-513. |
| 2. | Wu Fan, Zhao Su, Yu Bin, et al. A new coronavirus associated with human respiratory disease in China. Nature, 2020, 579(7798): 265-269. |
| 3. | Zhu Na, Zhang Dingyu, Wang Wenling, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med, 2020, 382(8): 727-733. |
| 4. | Li F, Li W H, Farzan M, et al. Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science, 2005, 309(5742): 1864-1868. |
| 5. | Agnihothram S, Gopal R, Yount B L, et al. Evaluation of serologic and antigenic relationships between middle eastern respiratory syndrome coronavirus and other coronaviruses to develop vaccine platforms for the rapid response to emerging coronaviruses. J Infect Dis, 2014, 209(7): 995-1006. |
| 6. | Li Wenhui, Michael J M, Vasilieva N, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature, 2003, 426(6965): 450-454. |
| 7. | Park W B, Kwon N J, Choi S J, et al. Virus isolation from the first patient with SARS-CoV-2 in Korea. J Korean Med Sci, 2020, 35(7): e84. |
| 8. | Du Lanying, Yang Yang, Zhou Yusen, et al. MERS-CoV spike protein: a key target for antivirals. Expert Opin Ther Targets, 2017, 21(2): 131-143. |
| 9. | Thanh L T, Andreadakis Z, Kumar A, et al. The COVID-19 vaccine development landscape. Nat Rev Drug Discov, 2020, 19(5): 305-306. |
| 10. | 白仲虎. 昕然, 王榮斌 哺乳動物細胞生產人用滅活疫苗相關技術進展. 中國細胞生物學學報, 2019, 41(10): 1986-1993. |
| 11. | 姚昕, 毛群穎, 梁爭論. EV71 全病毒滅活疫苗的研究進展. 中國生物制品學雜志, 2012, 25(10): 1391-1394. |
| 12. | Lin Jiangtao, Zhang Jiansan, Su Nan, et al. Safety and immunogenicity from a phase I trial of inactivated severe acute respiratory syndrome coronavirus vaccine. Antivir Ther, 2007, 12(7): 1107-1113. |
| 13. | 中國臨床試驗注冊中心. 新型冠狀病毒滅活疫苗(Vero 細胞)隨機、雙盲、安慰劑平行對照Ⅰ/Ⅱ期臨床試驗. (2020-04-11)[2020-04-13]. http://www.chictr.org.cn/showproj.aspx?proj=52227. |
| 14. | 中國臨床試驗注冊中心. 新型冠狀病毒(2019-CoV)滅活疫苗(Vero 細胞)Ⅰ/Ⅱ期臨床試驗. (2020-04-29) [2020-05-04]. http://www.chictr.org.cn/showproj.aspx?proj=53003. |
| 15. | 臨床試驗數據庫. Safety and Immunogenicity Study of Inactivated Vaccine for Prophylaxis of SARS CoV-2 Infection (COVID-19). (2020-4-20) [2020-04-28]. https://clinicaltrials.gov/ct2/show/NCT04352608?term=NCT04352608&draw=2&rank=1. |
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| 22. | Jimenez-Guarde?o J M, Regla-Nava J A, Nieto-Torres J L, et al. Identification of the mechanisms causing reversion to virulence in an attenuated SARS-CoV for the design of a genetically stable vaccine. PLoS Pathog, 2015, 11(10): e1005215. |
| 23. | 三葉草公司官網. Clover Successfully Produced 2019-nCoV Subunit Vaccine Candidate and Detected Cross-Reacting Antibodies from Sera of Multiple Infected Patients. (2020-02-10) [2020-02-10]. http://www.cloverbiopharma.com/index.php?m=content&c=index&a=show&catid=11&id=41. |
| 24. | 郭慧敏, 繆秋紅, 譚永貴, 等. 病毒樣顆粒的常用表達系統和應用進展. 中國動物傳染病學報, 2017, 25(4): 82-86. |
| 25. | Fochesato M, Dendouga N, Boxus M. Comparative preclinical evaluation of AS01 versus other adjuvant systems in a candidate herpes zoster glycoprotein E subunit vaccine. Hum Vaccin Immunother, 2016, 12(8): 2092-2095. |
| 26. | 葛蘭素史克公司官網(中文). 葛蘭素史克與養生堂廈門萬泰聯合廈門大學合作研發2019冠狀病毒疫苗. (2020-04-03) [2020-04-03]. https://www.gsk-china.com/zh-cn/media/press-releases/2020/葛蘭素史克與養生堂廈門萬泰聯合廈門大學合作研發2019冠狀病毒疫苗/. |
| 27. | 成傳剛, 慕婷, 袁軍, 等. 重組病毒載體疫苗研究進展. 中國病毒病雜志, 2018, 8(4): 318-328. |
| 28. | Redoni M, Yacoub S, Rivino L. Dengue: status of current and under-development vaccines. Rev Med Virol, 2020, 4: e2101. |
| 29. | Scott A H, Rituparna D, Matthew T O, et al. Immunogenicity, lot consistency, and extended safety of rVSVΔG-ZEBOV-GP vaccine: a phase 3 randomized, double-blind, placebo-controlled study in healthy adults. J Infect Dis, 2019, 220(7): 1127-1135. |
| 30. | Li Jingxin, Hou Lihua, Meng Fanyue, et al. Immunity duration of a recombinant adenovirus type-5 vector-based Ebola vaccine and a homologous prime-boost immunisation in healthy adults in China: final report of a randomised, double-blind, placebo-controlled, phase 1 trial. The Lancet Global Health, 2017, 5(3): e324-e334. |
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| 35. | Malczyk A H, Kupke A, Prüfer P, et al. A highly immunogenic and protective Middle East respiratory syndrome coronavirus vaccine based on a recombinant measles virus vaccine platform. Journal of Virology, 2015, 89(22): 11654-11667. |
| 36. | Humphreys I R, Sebastian S. Novel viral vectors in infectious diseases. Immunology, 2018, 153(1): 1-9. |
| 37. | Kichaev G, Mendoza J M, Amante D, et al. Electroporation mediated DNA vaccination directly to a mucosal surface results in improved immune responses. Hum Vaccin Immunother, 2013, 9(10): 2041-2048. |
| 38. | 宋麗, 熊丹, 焦新安, 等. 聚乙烯亞胺作為核酸疫苗佐劑的研究進展. 中國人獸共患病學報, 2019, 35(7): 660-666, 671. |
| 39. | 傅連臣, 劉靈芝, 侯佩強. DNA 疫苗研究進展. 預防醫學論壇, 2019, 25(10): 797-800. |
| 40. | 臨床試驗數據庫. Safety, tolerability and immunogenicity of INO-4800 for COVID-19 in healthy volunteers. (2020-04-07) [2020-04-24]. https://clinicaltrials.gov/ct2/show/NCT04336410?term=INO-4800&draw=2&rank=1. |
| 41. | Modjarrad K, Roberts C C, Mills K T, et al. Safety and immunogenicity of an anti-Middle East respiratory syndrome coronavirus DNA vaccine: a phase 1, open-label, single-arm, dose-escalation trial. Lancet Infect Dis, 2019, 19(9): 1013-1022. |
| 42. | Kutzler M A, Weiner D B. DNA vaccines: ready for prime time?. Nat Rev Genet, 2008, 9(10): 776-788. |
| 43. | Kowalski P S, Rudra A, Miao L, et al. Delivering the messenger: advances in technologies for therapeutic mRNA delivery. Molecular Therapy, 2019, 27(4): 710-728. |
| 44. | Pardi N, Hogan M J, Weissman D. Recent advances in mRNA vaccine technology. Curr Opin Immunol, 2020, 65: 14-20. |
| 45. | 臨床試驗數據庫. Safety and immunogenicity study of 2019-nCov vaccine (mRNA-1273) to treat novel coronavirus. (2020-2-25) [2020-05-04]. https://clinicaltrials.gov/ct2/show/NCT04283461?term=mRNA1273&draw=2&rank=1. |
| 46. | 臨床試驗數據庫. Study to describe the safety, tolerability, immunogenicity, and potential efficacy of RNA vaccine candidates against COVID-19 in healthy ddults. (2020-4-30) [2020-05-07]. https://clinicaltrials.gov/ct2/show/NCT04368728?term=BNT162&draw=2&rank=1. |
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| 50. | Czub M, Weingartl H, Czub S, et al. Evaluation of modified vaccinia virus Ankara based recombinant SARS vaccine in ferrets. Vaccine, 2005, 23(17/18): 2273-2279. |
| 51. | Román M, Calhoun W, Hinton K, et al. Respiratory syncytial virus infection in infants is associated with predominant Th-2-like response. Am J Respir Crit Care Med, 1997, 156(1): 190-195. |
| 52. | Tseng C T, Sbrana E, Iwata-Yoshikawa N, et al. Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. PLoS One, 2012, 7(4): e35421. |
| 53. | Yasui F, Kai C, Kitabatake M, et al. Prior immunization with severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) nucleocapsid protein causes severe pneumonia in mice infected with SARS-CoV. The Journal of Immunology, 2008, 181(9): 6337-6348. |
| 54. | Bolles M, Deming D, Long K, et al. A Double-Inactivated severe acute respiratory syndrome coronavirus vaccine provides incomplete protection in mice and induces increased eosinophilic proinflammatory pulmonary response upon challenge. Journal of Virology, 2011, 85(23): 12201-12215. |
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- 1. Chen Nanshan, Zhou Min, Dong Xuan, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet, 2020, 395(1223): 507-513.
- 2. Wu Fan, Zhao Su, Yu Bin, et al. A new coronavirus associated with human respiratory disease in China. Nature, 2020, 579(7798): 265-269.
- 3. Zhu Na, Zhang Dingyu, Wang Wenling, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med, 2020, 382(8): 727-733.
- 4. Li F, Li W H, Farzan M, et al. Structure of SARS coronavirus spike receptor-binding domain complexed with receptor. Science, 2005, 309(5742): 1864-1868.
- 5. Agnihothram S, Gopal R, Yount B L, et al. Evaluation of serologic and antigenic relationships between middle eastern respiratory syndrome coronavirus and other coronaviruses to develop vaccine platforms for the rapid response to emerging coronaviruses. J Infect Dis, 2014, 209(7): 995-1006.
- 6. Li Wenhui, Michael J M, Vasilieva N, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature, 2003, 426(6965): 450-454.
- 7. Park W B, Kwon N J, Choi S J, et al. Virus isolation from the first patient with SARS-CoV-2 in Korea. J Korean Med Sci, 2020, 35(7): e84.
- 8. Du Lanying, Yang Yang, Zhou Yusen, et al. MERS-CoV spike protein: a key target for antivirals. Expert Opin Ther Targets, 2017, 21(2): 131-143.
- 9. Thanh L T, Andreadakis Z, Kumar A, et al. The COVID-19 vaccine development landscape. Nat Rev Drug Discov, 2020, 19(5): 305-306.
- 10. 白仲虎. 昕然, 王榮斌 哺乳動物細胞生產人用滅活疫苗相關技術進展. 中國細胞生物學學報, 2019, 41(10): 1986-1993.
- 11. 姚昕, 毛群穎, 梁爭論. EV71 全病毒滅活疫苗的研究進展. 中國生物制品學雜志, 2012, 25(10): 1391-1394.
- 12. Lin Jiangtao, Zhang Jiansan, Su Nan, et al. Safety and immunogenicity from a phase I trial of inactivated severe acute respiratory syndrome coronavirus vaccine. Antivir Ther, 2007, 12(7): 1107-1113.
- 13. 中國臨床試驗注冊中心. 新型冠狀病毒滅活疫苗(Vero 細胞)隨機、雙盲、安慰劑平行對照Ⅰ/Ⅱ期臨床試驗. (2020-04-11)[2020-04-13]. http://www.chictr.org.cn/showproj.aspx?proj=52227.
- 14. 中國臨床試驗注冊中心. 新型冠狀病毒(2019-CoV)滅活疫苗(Vero 細胞)Ⅰ/Ⅱ期臨床試驗. (2020-04-29) [2020-05-04]. http://www.chictr.org.cn/showproj.aspx?proj=53003.
- 15. 臨床試驗數據庫. Safety and Immunogenicity Study of Inactivated Vaccine for Prophylaxis of SARS CoV-2 Infection (COVID-19). (2020-4-20) [2020-04-28]. https://clinicaltrials.gov/ct2/show/NCT04352608?term=NCT04352608&draw=2&rank=1.
- 16. 李征, 劉曄, 李春陽. 減毒活疫苗的應用及其研究進展. 中國生物制品學雜志, 2018, 31(2): 205-209.
- 17. Minor P D. Live attenuated vaccines: historical successes and current challenges. Virology, 2015, 479-480(5): 379-392.
- 18. Lam T T Y, Shum M H H, Zhu H C, et al. Identifying SARS-CoV-2 related coronaviruses in malayan pangolins, Nature, 2020, 5. DOI: 10.1038/s41586-020-2169-0.
- 19. Brunham R C, Coombs K M. In celebration of the 200th anniversary of Edward Jenner’s inquiry into the causes and effects of the variolae vaccinae. Can J Infect Dis, 1998, 9(5): 310-313.
- 20. Dediego M L, A?lvarez E, Almazan F, et al. A severe acute respiratory syndrome coronavirus that lacks the E gene is attenuated in vitro and in vivo. Journal of Virology, 2007, 81(4): 1701-1713.
- 21. Regla-Nava J A, Nieto-Torres J L, Jimenez-Guarde?o J M, et al. Severe acute respiratory syndrome coronaviruses with mutations in the E protein are attenuated and promising vaccine candidates. Journal of Virology, 2015, 89(7): 3870-3887.
- 22. Jimenez-Guarde?o J M, Regla-Nava J A, Nieto-Torres J L, et al. Identification of the mechanisms causing reversion to virulence in an attenuated SARS-CoV for the design of a genetically stable vaccine. PLoS Pathog, 2015, 11(10): e1005215.
- 23. 三葉草公司官網. Clover Successfully Produced 2019-nCoV Subunit Vaccine Candidate and Detected Cross-Reacting Antibodies from Sera of Multiple Infected Patients. (2020-02-10) [2020-02-10]. http://www.cloverbiopharma.com/index.php?m=content&c=index&a=show&catid=11&id=41.
- 24. 郭慧敏, 繆秋紅, 譚永貴, 等. 病毒樣顆粒的常用表達系統和應用進展. 中國動物傳染病學報, 2017, 25(4): 82-86.
- 25. Fochesato M, Dendouga N, Boxus M. Comparative preclinical evaluation of AS01 versus other adjuvant systems in a candidate herpes zoster glycoprotein E subunit vaccine. Hum Vaccin Immunother, 2016, 12(8): 2092-2095.
- 26. 葛蘭素史克公司官網(中文). 葛蘭素史克與養生堂廈門萬泰聯合廈門大學合作研發2019冠狀病毒疫苗. (2020-04-03) [2020-04-03]. https://www.gsk-china.com/zh-cn/media/press-releases/2020/葛蘭素史克與養生堂廈門萬泰聯合廈門大學合作研發2019冠狀病毒疫苗/.
- 27. 成傳剛, 慕婷, 袁軍, 等. 重組病毒載體疫苗研究進展. 中國病毒病雜志, 2018, 8(4): 318-328.
- 28. Redoni M, Yacoub S, Rivino L. Dengue: status of current and under-development vaccines. Rev Med Virol, 2020, 4: e2101.
- 29. Scott A H, Rituparna D, Matthew T O, et al. Immunogenicity, lot consistency, and extended safety of rVSVΔG-ZEBOV-GP vaccine: a phase 3 randomized, double-blind, placebo-controlled study in healthy adults. J Infect Dis, 2019, 220(7): 1127-1135.
- 30. Li Jingxin, Hou Lihua, Meng Fanyue, et al. Immunity duration of a recombinant adenovirus type-5 vector-based Ebola vaccine and a homologous prime-boost immunisation in healthy adults in China: final report of a randomised, double-blind, placebo-controlled, phase 1 trial. The Lancet Global Health, 2017, 5(3): e324-e334.
- 31. 中國臨床試驗注冊中心. 重組新型冠狀病毒(2019-COV)疫苗(腺病毒載體)Ⅰ期臨床試驗. (2020-03-17) [2020-03-18]. http://www.chictr.org.cn/showproj.aspx?proj=51154.
- 32. 中國臨床試驗注冊中心. 重組新型冠狀病毒(2019-nCOV)疫苗(腺病毒載體)隨機、雙盲、安慰劑對照設計的Ⅱ期臨床試驗. (2020-4-10) [2020-04-10]. http://www.chictr.org.cn/showproj.aspx?proj=52006.
- 33. 臨床試驗數據庫. A Study of a Candidate COVID-19 Vaccine (COV001). (2020-03-27) [2020-05-08]. https://clinicaltrials.gov/ct2/show/NCT04324606?term=NCT04324606&draw=2&rank=1.
- 34. Mühlebach M D. Vaccine platform recombinant measles virus. Virus Genes, 2017, 53(5): 733-740.
- 35. Malczyk A H, Kupke A, Prüfer P, et al. A highly immunogenic and protective Middle East respiratory syndrome coronavirus vaccine based on a recombinant measles virus vaccine platform. Journal of Virology, 2015, 89(22): 11654-11667.
- 36. Humphreys I R, Sebastian S. Novel viral vectors in infectious diseases. Immunology, 2018, 153(1): 1-9.
- 37. Kichaev G, Mendoza J M, Amante D, et al. Electroporation mediated DNA vaccination directly to a mucosal surface results in improved immune responses. Hum Vaccin Immunother, 2013, 9(10): 2041-2048.
- 38. 宋麗, 熊丹, 焦新安, 等. 聚乙烯亞胺作為核酸疫苗佐劑的研究進展. 中國人獸共患病學報, 2019, 35(7): 660-666, 671.
- 39. 傅連臣, 劉靈芝, 侯佩強. DNA 疫苗研究進展. 預防醫學論壇, 2019, 25(10): 797-800.
- 40. 臨床試驗數據庫. Safety, tolerability and immunogenicity of INO-4800 for COVID-19 in healthy volunteers. (2020-04-07) [2020-04-24]. https://clinicaltrials.gov/ct2/show/NCT04336410?term=INO-4800&draw=2&rank=1.
- 41. Modjarrad K, Roberts C C, Mills K T, et al. Safety and immunogenicity of an anti-Middle East respiratory syndrome coronavirus DNA vaccine: a phase 1, open-label, single-arm, dose-escalation trial. Lancet Infect Dis, 2019, 19(9): 1013-1022.
- 42. Kutzler M A, Weiner D B. DNA vaccines: ready for prime time?. Nat Rev Genet, 2008, 9(10): 776-788.
- 43. Kowalski P S, Rudra A, Miao L, et al. Delivering the messenger: advances in technologies for therapeutic mRNA delivery. Molecular Therapy, 2019, 27(4): 710-728.
- 44. Pardi N, Hogan M J, Weissman D. Recent advances in mRNA vaccine technology. Curr Opin Immunol, 2020, 65: 14-20.
- 45. 臨床試驗數據庫. Safety and immunogenicity study of 2019-nCov vaccine (mRNA-1273) to treat novel coronavirus. (2020-2-25) [2020-05-04]. https://clinicaltrials.gov/ct2/show/NCT04283461?term=mRNA1273&draw=2&rank=1.
- 46. 臨床試驗數據庫. Study to describe the safety, tolerability, immunogenicity, and potential efficacy of RNA vaccine candidates against COVID-19 in healthy ddults. (2020-4-30) [2020-05-07]. https://clinicaltrials.gov/ct2/show/NCT04368728?term=BNT162&draw=2&rank=1.
- 47. Pardi N, Hogan M J, Porter F W, et al. mRNA vaccines-a new era in vaccinology. Nat Rev Drug Discov, 2018, 17(4): 261-279.
- 48. World Health Organization. A coordinated global research roadmap: 2019 novel coronavirus. (2020-03-12) [2020-03-12]. https://www.who.int/who-documents-detail/a-coordinated-global-research-roadmap.
- 49. Weingartl H, Czub M, Czub S, et al. Immunization with modified vaccinia virus Ankara-based recombinant vaccine against severe acute respiratory syndrome is associated with enhanced hepatitis in ferrets. Journal of Virology, 2004, 78(22): 12672-12676.
- 50. Czub M, Weingartl H, Czub S, et al. Evaluation of modified vaccinia virus Ankara based recombinant SARS vaccine in ferrets. Vaccine, 2005, 23(17/18): 2273-2279.
- 51. Román M, Calhoun W, Hinton K, et al. Respiratory syncytial virus infection in infants is associated with predominant Th-2-like response. Am J Respir Crit Care Med, 1997, 156(1): 190-195.
- 52. Tseng C T, Sbrana E, Iwata-Yoshikawa N, et al. Immunization with SARS coronavirus vaccines leads to pulmonary immunopathology on challenge with the SARS virus. PLoS One, 2012, 7(4): e35421.
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