Abstract：Since coronavirus disease 2019 (COVID-19) broke out, the world has accelerated the development of preventive vaccines. By December 2020, 60 candidate vaccines have been approved for clinical trials, of which 7 vaccines, including 3 inactivated vaccines, 2 mRNA vaccines and 2 vector vaccines, have been authorized for emergency use or conditional marketing. In this paper, we reviewed the development progress in inactivated vaccines, nucleic acid vaccines, vector vaccines, protein subunit vaccines, attenuated vaccines and virus-like particle vaccines, as well as advantages and disadvantages of these vaccines. The studies showed that the vaccines against COVID-19 in phase III clinical trials had good safety and immunogenicity, and those authorized vaccines were declared to have good efficacy. However, attention should be paid to the adverse reactions of the vaccines and the long-term protective effects, in order to improve the immunization strategy for the control of COVID-19 epidemic.
[1] World Health Organization.Coronavirus disease (COVID-19) pandemic[EB/OL].[2021-01-07]. https://www.who.int/emergencies/diseases/novel-coronavirus-2019. [2] DAI L,GAO G F. Viral targets for vaccines against COVID-19[J/OL]. Nat Rev Immunol(2020-12-18) [2021-01-07].https://www.nature.com/articles/s41577-020-00480-0.DOI: 10.1038/s41577-020-00480-0. [3] World Health Organization.DRAFT landscape of COVID-19 candidate vaccines[EB/OL]. [2021-01-07].https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines. [4] 邓强,王子晨,吴沁,等. 新型冠状病毒疫苗的研究进展[J]. 暨南大学学报(自然科学与医学版),2020,41(6):511-519. [5] MULLIGAN M J.An inactivated virus candidate vaccine to prevent COVID-19[J]. JAMA,2020,324(10):943-945. [6] KAUR S P,GUPTA V. COVID-19 vaccine:a comprehensive status report[J/OL]. Virus Res,2020,288[2021-01-07].https://www.researchgate.net/publication/343630942_COVID-19_Vaccine_A_comprehensive_status_report.DOI:10.1016/j.virusres.2020. 198114. [7] 甄永苏,赵铠. 疫苗研究与应用[M]. 北京:人民卫生出版社,2013. [8] XIA S,ZHANG Y,WANG Y,et al.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,2020,21(1):39-51. [9] ZHANG Y,ZENG G,PAN H,et al. 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/OL]. Lancet Infect Dis(2020-11-17)[2021-01-07].https://www.sciencedirect.com/science/article/pii/S1473309920308434. [10] UAE Ministry of Health and Prevention announces official registration of inactivated COVID-19 vaccine used in #4Humanity Trials[EB/OL].(2020-12-09)[2021-01-07]. http://www.wam.ae/ar/details/1395302893588. [11] 国务院新闻办公室. 国务院联防联控机制举行新冠病毒疫苗附条件上市及相关工作情况发布会[EB/OL].[2021-01-07]. http://www.scio.gov.cn/xwfbh/xwbfbh/wqfbh/42311/44679/index.htm. [12] KUTZLER M A,WEINER D B.DNA vaccines:ready for prime time?[J]. Nat Rev Genet,2008,9(10):776-788. [13] PARDI N,HOGAN M J,PORTER F W,et al.mRNA vaccines-a new era in vaccinology[J]. Nat Rev Drug Discov,2018,17(4):261-279. [14] SUSCHAK J J,WILLIAMS J A,SCHMALJOHN C S.Advancements in DNA vaccine vectors,non-mechanical delivery methods,and molecular adjuvants to increase immunogenicity[J]. Human Vaccines Immunother,2017,13(12):2837-2848. [15] MASCOLA J R,FAUCI A S.Novel vaccine technologies for the 21st century[J]. Nat Rev Immunol,2020,20(2):87-88. [16] POLACK F P,THOMAS S J,KITCHIN N,et al.Safety and efficacy of the BNT162b2 mRNA covid-19 vaccine[J]. N Engl J Med,2020,383(27):2603-2615. [17] BADEN L R,EL SAHLY H M,ESSINK B,et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine[J/OL]. N Engl J Med(2020-12-30)[2021-01-07].https://www.researchgate.net/publication/348086310_Efficacy_and_Safety_of_the_mRNA-1273_SARS-CoV-2_Vaccine.DOI:10.1056/NEJMoa2035389. [18] WIDGE A T,ROUPHAEL N G,JACKSON L A,et al.Durability of responses after SARS-CoV-2 mRNA-1273 vaccination [J/OL]. N Engl J Med,384(1):80-82. [19] Food and Drug Administration. Vaccines and Related Biological Products Advisory Committee Meeting December 10,2020-FDA[EB/OL]. [2021-01-07]. https://www.fda.gov/media/144245/download. [20] Food and Drug Administration. COVID-19 vaccines authorized for emergency use[EB/OL].[2021-01-07].https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/covid-19-vaccines. [21] INOVIO announces initiation of phase 2 segment of its phase 2/3 clinical trial for its COVID-19 DNA vaccine candidate,INO-4800;trial will be funded by the U.S.Department of Defense[EB/OL]. [2021-01-07].http://ir.inovio.com/news-releases/news-releases-details/2020/INOVIO-Announces-Initiation-of-Phase-2-Segment-of-its-Phase-23-Clinical-Trial-for-its-COVID-19-DNA-Vaccine Candidate-INO-4800-Trial-Will-Be-Funded-by-the-U.S.-Department-of-Defense/default.aspx. [22] INOVIO announces positive interim phase 1 data for INO-4800 vaccine for COVID-19[EB/OL]. [2021-01-07].http://ir.inovio.com/news-releases/news-releases-details/2020/INOVIO-Announces-Positive-Interim-Phase-1-Data-For-INO-4800-Vaccine for-COVID-19/default.aspx. [23] Safety,immunogenicity,and efficacy of INO-4800 for COVID-19 in healthy seronegative adults at high risk of SARS-CoV-2 exposure[EB/OL].[2021-01-07].https://clinicaltrials.gov/ct2/show/NCT04642638. [24] 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. [25] 柳云帆. 一种新的复制缺陷型腺病毒载体系统的组建[D].北京:中国疾病预防控制中心,2011. [26] AZD1222 vaccine met primary efficacy endpoint in preventing COVID-19[EB/OL]. [2021-01-07].https://www.astrazeneca.com/media-centre/press-releases/2020/azd1222hlr.html. [27] Merck＇s ERVEBO® [Ebola Zaire Vaccine (rVSVΔG-ZEBOV-GP) live] granted conditional approval in the European Union[EB/OL]. [2021-01-07].https://www.businesswire.com/news/home/20191111005601/en/Merck%E2%80%99s-ERVEBO%C2%AE-Ebola-Zaire-Vaccine-rVSV%CE%94G-ZEBOV-GP-live. [28] 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,placebo-controlled,phase 2 trial[J]. Lancet,2020,396(10249):479-488. [29] 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,397(10269):99-111. [30] Sputnik V Press Releases[EB/OL]Sputnik V Press Releases[EB/OL]. [2021-01-07]. https://sputnikvaccine.com/newsroom/pressreleases/. [31] SADOFF J,LE GARS M,SHUKAREV G,et al. Safety and immunogenicity of the Ad26.COV2.S COVID-19 vaccine candidate:interim results 1 of a phase 1/2a,double-blind,randomized,placebo-controlled trial[EB/OL].[2021-01-07].https://doi.org/10.1101/2020.09.23.20199604. [32] 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):3030-3040. [33] 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):2320-2332. [34] YANG S L,LI Y,DAI L P,et al. 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[EB/OL].[2021-01-07].https://doi.org/10.1101/2020.12.20.20248602. [35] 李焱琳. 病毒样颗粒疫苗的免疫机制研究及应用进展[J]. 国际生物制品学杂志,2019,42(4): 203-208. [36] 郭慧敏,缪秋红,谭永贵,等. 病毒样颗粒的常用表达系统和应用进展[J]. 中国动物传染病学报,2017,25(4):82-86. [37] WARD B J,GOBEIL P,SÉGUIN A,et al. Phase 1 trial of a candidate recombinant virus-like particle vaccine for Covid-19 disease produced in plants. [EB/OL].[2021-01-07].https://doi.org/10.1101/2020.11.04.20226282. [38] GARBER K. Coronavirus vaccine developers wary of errant antibodies[J/OL]. Nat Biotechnol(2020-06-05)[2021-01-07].https://www.researchgate.net/publication/341951939_Coronavirus_vaccine_developers_wary_of_errant_antibodies.DOI:10.1038/d41587-020-00016-w. [39] AGRAWAL A S,TAO X,ALGAISSI A,et al.Immunization with inactivated Middle East respiratory syndrome coronavirus vaccine leads to lung immunopathology on challenge with live virus[J]. Human Vaccines Immunother,2016,12(9):2351-2356. [40] WAN Y,SHANG J,SUN S,et al. Molecular mechanism for antibody-dependent enhancement of coronavirus entry[J/OL]. J Virol,2020,94(5)[2021-01-07].https://www.researchgate.net/publication/337899543_Molecular_Mechanism_for_Antibody-Dependent_Enhancement_of_Coronavirus_Entry.DOI:10.1128/JVI. 02015-19. [41] 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,2020,395(10240):1845-1854. [42] 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 aphase 1/2,single-blind,randomised controlled trial[J]. Lancet,2020,396(10249):467-478. [43] World Health Organization.WHO target product profiles for COVID-19 vaccines[R]. Geneva:World Health Organization,2020. [44] HODGSON S H,MANSATTA K,MALLETT G,et al. What defines an efficacious COVID-19 vaccine? A review of the challenges assessing the clinical efficacy of vaccines against SARS-CoV-2[J/OL]. Lancet Infect Dis(2020-10-27)[2021-01-07].https://doi.org/10.1016/S1473-3099(20)30773-8. [45] Pfizer and BioNTech celebrate historic first authorization in the U.S. of vaccine to prevent COVID-19[EB/OL]. (2020-12-31)[2021-01-07]. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-celebrate-historic-first-authorization. [46] Moderna＇s COVID-19 vaccine candidate meets its primary efficacy endpoint in the first interim analysis of the Phase 3 COVE Study[EB/OL]. (2020-12-02)[2021-01-07]. https://investors.modernatx.com/news-releases/news-release-details/modernas-covid-19-vaccine-candidate-meets-its-primary-efficacy. [47] 我国5家正进行Ⅲ期临床试验的疫苗企业的产能将共达到20亿剂[EB/OL]. (2020-12-31)[2021-01-07]. https://news.sina.com.cn/o/2020-12-19/doc-iiznctke7398414.shtml. [48] THANH LE T,ANDREADAKIS Z,KUMAR A, et al.The COVID-19 vaccine development landscape[J]. Nat Rev Drug Discov,2020,19(5):305-306. [49] GRUBAUGH N D,HANAGE W P,RASMUSSEN A L.Making sense of mutation:what D614G means for the COVID-19 pandemic remains unclear[J]. Cell,2020,182(4):794-795.
