Progress on the development of the SARS-CoV-2 vaccine and antibody drugs_Journal of Biomedical Engineering

Authors：

XU Siyu ¹ ,  TANG Dan ²

1. Operation Management Office, West China Second University Hospital, Chengdu 610065, P. R. China;
2. Department of Urology, West China Hospital of Sichuan University, Chengdu 610065, P. R. China;

Corresponding author：

Keywords：

SARS-CoV-2; Vaccine; Antibody; Genetic engineering; Spike

DOI：

10.7507/1001-5515.202207063

Video：

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The raging global epidemic of coronavirus disease 2019 (COVID-19) not only poses a major threat to public health, but also has a huge impact on the global health care system and social and economic development. Therefore, accelerating the development of vaccines and antibody drugs to provide people with effective protection and treatment measures has become the top priority of researchers and medical institutions in the field. At present, several vaccines and antibody drugs targeting SARS-Cov-2 have been in the stage of clinical research or approved for marketing around the world. In this manuscript, we summarized the vaccines and antibody drugs which apply genetic engineering technologies to target spike protein, including subunit vaccines, viral vector vaccines, DNA vaccines, mRNA vaccines, and several neutralizing antibody drugs, and discussed the trends of vaccines and antibody drugs in the future.

Citation： XU Siyu, TANG Dan. Progress on the development of the SARS-CoV-2 vaccine and antibody drugs. Journal of Biomedical Engineering, 2022, 39(5): 1059-1064. doi: 10.7507/1001-5515.202207063 Copy

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2.	Samrat S K, Tharappel A M, Li Z, et al. Prospect of SARS-CoV-2 spike protein: potential role in vaccine and therapeutic development. Virus Res, 2020, 288: 198141.
3.	Creech C B, Walker S C, Samuels R J. SARS-CoV-2 vaccines. JAMA, 2021, 325(13): 1318-1320.
4.	Weinreich D M, Sivapalasingam S, Norton T, et al. REGN-COV2, a neutralizing antibody cocktail, in outpatients with Covid-19. N Engl J Med, 2021, 384(3): 238-251.
5.	Wrapp D, Wang N, Corbett K S, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science, 2020, 367(6483): 1260-1263.
6.	Walls A C, Park Y J, Tortorici M A, et al. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell, 2020, 181(2): 281-292.
7.	Yan R, Zhang Y, Li Y, et al. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science, 2020, 367(6485): 1444-1448.
8.	Jarząb A, Skowicki M, Witkowska D. Subunit vaccines–antigens, carriers, conjugation methods and the role of adjuvants. Postepy Hig Med Dosw, 2013, 67: 1128-1143.
9.	杨利敏, 田德雨, 刘文军. 新型冠状病毒疫苗研究策略分析. 生物工程学报, 2020, 36(4): 593-604.
10.	Yan R, Zhang Y, Li Y, et al. Structural basis for the different states of the spike protein of SARS-CoV-2 in complex with ACE2. Cell Res, 2021, 31(6): 717-719.
11.	Black M, Trent A, Tirrell M, et al. Advances in the design and delivery of peptide subunit vaccines with a focus on toll-like receptor agonists. Expert Rev Vaccines, 2010, 9(2): 157-173.
12.	Pallesen J, Wang N, Corbett K S, et al. Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen. Proc Natl Acad Sci U S A, 2017, 114(35): E7348-E7357.
13.	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. Lancet Respir Med, 2021, 9(12): 1396-1406.
14.	Dai L, Gao L, Tao L, et al. Efficacy and safety of the RBD-dimer-based Covid-19 vaccine ZF2001 in adults. N Engl J Med, 2022, 386(22): 2097-2111.
15.	Robert-Guroff M. Replicating and non-replicating viral vectors for vaccine development. Curr Opin Biotechnol, 2007, 18(6): 546-556.
16.	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. Lancet, 2020, 395(10240): 1845-1854.
17.	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. Lancet, 2021, 397(10269): 99-111.
18.	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. Lancet, 2020, 396(10249): 467-478.
19.	Fomsgaard A, Liu M A. The key role of nucleic acid vaccines for one health. Viruses, 2021, 13(2): 258.
20.	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. Lancet, 2022, 399(10332): 1313-1321.
21.	Ura T, Yamashita A, Mizuki N, et al. New vaccine production platforms used in developing SARS-CoV-2 vaccine candidates. Vaccine, 2021, 39(2): 197-201.
22.	Baden L R, El Sahly H M, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med, 2021, 384(5): 403-416.
23.	Li J, Hui A, Zhang X, et al. Safety and immunogenicity of the SARS-CoV-2 BNT162b1 mRNA vaccine in younger and older Chinese adults: a randomized, placebo-controlled, double-blind phase 1 study. Nat Med, 2021, 27(6): 1062-1070.
24.	Brito L A, Kommareddy S, Maione D, et al. Self-amplifying mRNA vaccines. Adv Genet, 2015, 89: 179-233.
25.	Ndeupen S, Qin Z, Jacobsen S, et al. The mRNA-LNP platform's lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory. iScience, 2021, 24(12): 103479.
26.	史瑞, 严景华. 抗新型冠状病毒单克隆中和抗体药物研发进展. 中国生物工程杂志, 2021, 41(6): 129-135.
27.	Li D, Sempowski G D, Saunders K O, et al. SARS-CoV-2 neutralizing antibodies for COVID-19 prevention and treatment. Annu Rev Med, 2022, 73: 1-16.
28.	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. Cell, 2020, 181(2): 271-280.
29.	Piccoli L, Park Y-J, Tortorici M A, et al. Mapping neutralizing and immunodominant sites on the SARS-CoV-2 Spike receptor-binding domain by structure-guided high-resolution serology. Cell, 2020, 183(4): 1024-1042.
30.	Hansen J, Baum A, Pascal K E, et al. Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail. Science, 2020, 369(6506): 1010-1014.
31.	Chen P, Nirula A, Heller B, et al. SARS-CoV-2 neutralizing antibody LY-CoV555 in outpatients with Covid-19. N Engl J Med, 2020, 384(3): 229-237.
32.	马亦林. 抗2019-nCoV的单克隆抗体作用机制及其制剂研究进展. 中华临床感染病杂志, 2021, 14(2): 91-96.
33.	Shi R, Shan C, Duan X, et al. A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2. Nature, 2020, 584(7819): 120-124.
34.	Gottlieb R L, Nirula A, Chen P, et al. Effect of bamlanivimab as monotherapy or in combination with etesevimab on viral load in patients with mild to moderate COVID-19: a randomized clinical trial. JAMA, 2021, 325(7): 632-644.
35.	Ju B, Zhang Q, Ge J, et al. Human neutralizing antibodies elicited by SARS-CoV-2 infection. Nature, 2020, 584(7819): 115-119.
36.	Jones B E, Brown-Augsburger P L, Corbett K S, et al. The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates. Sci Transl Med, 2021, 13(593): eabf1906.
37.	McCallum M, De Marco A, Lempp F A, et al. N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2. Cell, 2021, 184(9): 2332-2347.
38.	Zost S J, Gilchuk P, Case J B, et al. Potently neutralizing and protective human antibodies against SARS-CoV-2. Nature, 2020, 584(7821): 443-449.
39.	Kim C, Ryu D K, Lee J, et al. A therapeutic neutralizing antibody targeting receptor binding domain of SARS-CoV-2 spike protein. Nat Commun, 2021, 12(1): 288.
40.	梁红远, 周旭. 抗新型冠状病毒中和抗体研究进展. 国际生物制品学杂志, 2021, 44(1): 1-6.
41.	Chi X, Yan R, Zhang J, et al. A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2. Science, 2020, 369(6504): 650-655.
42.	Suryadevara N, Shrihari S, Gilchuk P, et al. Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein. Cell, 2021, 184(9): 2316-2331.
43.	Li D, Edwards R J, Manne K, et al. In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies. Cell, 2021, 184(16): 4203-4219.
44.	Jennewein M F, MacCamy A J, Akins N R, et al. Isolation and characterization of cross-neutralizing coronavirus antibodies from COVID-19 subjects. Cell Rep, 2021, 36(2): 109353.
45.	Levin M J, Ustianowski A, De Wit S, et al. Intramuscular AZD7442 (tixagevimab-cilgavimab) for prevention of Covid-19. N Engl J Med, 2022, 386(23): 2188-2200.
46.	Loo Y M, McTamney P M, Arends R H, et al. The SARS-CoV-2 monoclonal antibody combination, AZD7442, is protective in nonhuman primates and has an extended half-life in humans. Sci Transl Med, 2022, 14(635): eabl8124.
47.	Cao Y, Wang J, Jian F, et al. Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies. Nature, 2022, 602(7898): 657-663.

1. Zhou P, Yang X L, Wang X G, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 2020, 579(7798): 270-273.
2. Samrat S K, Tharappel A M, Li Z, et al. Prospect of SARS-CoV-2 spike protein: potential role in vaccine and therapeutic development. Virus Res, 2020, 288: 198141.
3. Creech C B, Walker S C, Samuels R J. SARS-CoV-2 vaccines. JAMA, 2021, 325(13): 1318-1320.
4. Weinreich D M, Sivapalasingam S, Norton T, et al. REGN-COV2, a neutralizing antibody cocktail, in outpatients with Covid-19. N Engl J Med, 2021, 384(3): 238-251.
5. Wrapp D, Wang N, Corbett K S, et al. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science, 2020, 367(6483): 1260-1263.
6. Walls A C, Park Y J, Tortorici M A, et al. Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell, 2020, 181(2): 281-292.
7. Yan R, Zhang Y, Li Y, et al. Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2. Science, 2020, 367(6485): 1444-1448.
8. Jarząb A, Skowicki M, Witkowska D. Subunit vaccines–antigens, carriers, conjugation methods and the role of adjuvants. Postepy Hig Med Dosw, 2013, 67: 1128-1143.
9. 杨利敏, 田德雨, 刘文军. 新型冠状病毒疫苗研究策略分析. 生物工程学报, 2020, 36(4): 593-604.
10. Yan R, Zhang Y, Li Y, et al. Structural basis for the different states of the spike protein of SARS-CoV-2 in complex with ACE2. Cell Res, 2021, 31(6): 717-719.
11. Black M, Trent A, Tirrell M, et al. Advances in the design and delivery of peptide subunit vaccines with a focus on toll-like receptor agonists. Expert Rev Vaccines, 2010, 9(2): 157-173.
12. Pallesen J, Wang N, Corbett K S, et al. Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen. Proc Natl Acad Sci U S A, 2017, 114(35): E7348-E7357.
13. 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. Lancet Respir Med, 2021, 9(12): 1396-1406.
14. Dai L, Gao L, Tao L, et al. Efficacy and safety of the RBD-dimer-based Covid-19 vaccine ZF2001 in adults. N Engl J Med, 2022, 386(22): 2097-2111.
15. Robert-Guroff M. Replicating and non-replicating viral vectors for vaccine development. Curr Opin Biotechnol, 2007, 18(6): 546-556.
16. 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. Lancet, 2020, 395(10240): 1845-1854.
17. 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. Lancet, 2021, 397(10269): 99-111.
18. 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. Lancet, 2020, 396(10249): 467-478.
19. Fomsgaard A, Liu M A. The key role of nucleic acid vaccines for one health. Viruses, 2021, 13(2): 258.
20. 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. Lancet, 2022, 399(10332): 1313-1321.
21. Ura T, Yamashita A, Mizuki N, et al. New vaccine production platforms used in developing SARS-CoV-2 vaccine candidates. Vaccine, 2021, 39(2): 197-201.
22. Baden L R, El Sahly H M, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med, 2021, 384(5): 403-416.
23. Li J, Hui A, Zhang X, et al. Safety and immunogenicity of the SARS-CoV-2 BNT162b1 mRNA vaccine in younger and older Chinese adults: a randomized, placebo-controlled, double-blind phase 1 study. Nat Med, 2021, 27(6): 1062-1070.
24. Brito L A, Kommareddy S, Maione D, et al. Self-amplifying mRNA vaccines. Adv Genet, 2015, 89: 179-233.
25. Ndeupen S, Qin Z, Jacobsen S, et al. The mRNA-LNP platform's lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory. iScience, 2021, 24(12): 103479.
26. 史瑞, 严景华. 抗新型冠状病毒单克隆中和抗体药物研发进展. 中国生物工程杂志, 2021, 41(6): 129-135.
27. Li D, Sempowski G D, Saunders K O, et al. SARS-CoV-2 neutralizing antibodies for COVID-19 prevention and treatment. Annu Rev Med, 2022, 73: 1-16.
28. 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. Cell, 2020, 181(2): 271-280.
29. Piccoli L, Park Y-J, Tortorici M A, et al. Mapping neutralizing and immunodominant sites on the SARS-CoV-2 Spike receptor-binding domain by structure-guided high-resolution serology. Cell, 2020, 183(4): 1024-1042.
30. Hansen J, Baum A, Pascal K E, et al. Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail. Science, 2020, 369(6506): 1010-1014.
31. Chen P, Nirula A, Heller B, et al. SARS-CoV-2 neutralizing antibody LY-CoV555 in outpatients with Covid-19. N Engl J Med, 2020, 384(3): 229-237.
32. 马亦林. 抗2019-nCoV的单克隆抗体作用机制及其制剂研究进展. 中华临床感染病杂志, 2021, 14(2): 91-96.
33. Shi R, Shan C, Duan X, et al. A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2. Nature, 2020, 584(7819): 120-124.
34. Gottlieb R L, Nirula A, Chen P, et al. Effect of bamlanivimab as monotherapy or in combination with etesevimab on viral load in patients with mild to moderate COVID-19: a randomized clinical trial. JAMA, 2021, 325(7): 632-644.
35. Ju B, Zhang Q, Ge J, et al. Human neutralizing antibodies elicited by SARS-CoV-2 infection. Nature, 2020, 584(7819): 115-119.
36. Jones B E, Brown-Augsburger P L, Corbett K S, et al. The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates. Sci Transl Med, 2021, 13(593): eabf1906.
37. McCallum M, De Marco A, Lempp F A, et al. N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2. Cell, 2021, 184(9): 2332-2347.
38. Zost S J, Gilchuk P, Case J B, et al. Potently neutralizing and protective human antibodies against SARS-CoV-2. Nature, 2020, 584(7821): 443-449.
39. Kim C, Ryu D K, Lee J, et al. A therapeutic neutralizing antibody targeting receptor binding domain of SARS-CoV-2 spike protein. Nat Commun, 2021, 12(1): 288.
40. 梁红远, 周旭. 抗新型冠状病毒中和抗体研究进展. 国际生物制品学杂志, 2021, 44(1): 1-6.
41. Chi X, Yan R, Zhang J, et al. A neutralizing human antibody binds to the N-terminal domain of the Spike protein of SARS-CoV-2. Science, 2020, 369(6504): 650-655.
42. Suryadevara N, Shrihari S, Gilchuk P, et al. Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein. Cell, 2021, 184(9): 2316-2331.
43. Li D, Edwards R J, Manne K, et al. In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies. Cell, 2021, 184(16): 4203-4219.
44. Jennewein M F, MacCamy A J, Akins N R, et al. Isolation and characterization of cross-neutralizing coronavirus antibodies from COVID-19 subjects. Cell Rep, 2021, 36(2): 109353.
45. Levin M J, Ustianowski A, De Wit S, et al. Intramuscular AZD7442 (tixagevimab-cilgavimab) for prevention of Covid-19. N Engl J Med, 2022, 386(23): 2188-2200.
46. Loo Y M, McTamney P M, Arends R H, et al. The SARS-CoV-2 monoclonal antibody combination, AZD7442, is protective in nonhuman primates and has an extended half-life in humans. Sci Transl Med, 2022, 14(635): eabl8124.
47. Cao Y, Wang J, Jian F, et al. Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies. Nature, 2022, 602(7898): 657-663.

Journal of Biomedical Engineering

Progress on the development of the SARS-CoV-2 vaccine and antibody drugs

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