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1、Articleshad infected more than 4-7 million people across 215 countries or territories and killed more than 316000 worldwide.5In the absence of effective prevention measures, current management to control the epidemic is the enforcement of quarantine, isolation, and physical distancing.67 Effective v
2、accines against COVID-19 are urgently needed to reduce the enormous burden of mortality and morbidity associated with SARS-CoV-2 infection.8 There are more than 100 candidate vaccines in development worldwide,9 among them at least eight have started or will soonPublished OnlineMay 22, 2020 s:/doi.or
3、g/10.1016/ 50140-6736(20)31208-3Contributed equallyBeijing Institute of Biotechnology, Beijing, China (Prof W Chen PhD, ProfJ-JXu PhD, Prof L-H Hou PhD, S-PWu PhD, B-SWang PhD);NHCKey Laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing
4、, China (ProfF-C Zhu MSc, W-J Wang MSc, Prof J-X Li PhD,S-YJiaMPH, H-D Jiang BSc); China National Institute for Food and Drug Control, Beijing, China (ProfY-H Li PhD, Li Wang PhD); Hubei Provincial Center for Disease Control and Prevention, Wuhan, China (ProfX-H Guan PhD, ZWang MPH, LeWangMPH);Beiji
5、ng Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing, China (Prof T Jiang PhD.YHuPhD); CanSino Biologies, Tianjin, China (J-B Gou PhD); Clinical Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
6、, Wuhan, China (Prof W Wang PhD, Prof S-B Xu PhD); and Shanghai Canming Medical Technology, Shanghai, China (X-W Wang MD)Correspondence to: Prof Wei Chen, Beijing Institute of Biotechnology, Beijing 100071, China cw0226foxmail orProf Wei Wang, Clinical Research Center,Tongji Hospital, Tongji Medical
7、 College, Huazhong University of Science and Technology, Wuhan 430032, Chinawwangvip.126 Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trialFeng-Cai Zhu*, Yu-Hua Li*, Xu-Hua Guan, L
8、i-Hua Hou, Wen-Juan Wang, Jing-Xin Li, Shi-Po Wu, Bu-Sen Wang, Zhao Wang, Lei Wang, Si-YueJia, Hu-Dachuan Jiang, Ling Wang, Tao Jiang, Yi Hu, Jin-Bo Gou, Sha-Bei Xu, Jun-Jie Xu, Xue-Wen Wang, Wei Wang, Wei ChenSummaryBackground A vaccine to protect against COVID-19 is urgently needed. We aimed to as
9、sess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing the spike glycoprotein of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain.Methods We did a dose-escalation, single-centre, open-label, non-randomised,
10、 phase 1 trial of an Ad5 vectored COVID-19 vaccine in Wuhan, China. Healthy adults aged between 18 and 60 years were sequentially enrolled and allocated to one of three dose groups (5x10吗 1 x 1011, and 1-5 x 1011 viral particles) to receive an intramuscular injection of vaccine. The primary outcome
11、was adverse events in the 7 days post-vaccination. Safety was assessed over 28 days post-vaccination. Specific antibodies were measured with ELISA, and the neutralising antibody responses induced by vaccination were detected with SARS-CoV-2 virus neutralisation and pseudovirus neutralisation tests.
12、T-cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays. This study is registered with ClinicallYials.gov, NCT04313127.Findings Between March 16 and March 27,2020, we screened 195 individuals for eligibility. Of them, 108 participants (51% male, 49% female; mean age 36-3
13、 years) were recruited and received the low dose (n=36), middle dose (n=36), or high dose (n=36) of the vaccine. All enrolled participants were included in the analysis. At least one adverse reaction within the first 7 days after the vaccination was reported in 30 (83%) participants in the low dose
14、group, 30 (83%) participants in the middle dose group, and 27 (75%) participants in the high dose group. The most common injection site adverse reaction was pain, which was reported in 58 (54%) vaccine recipients, and the most commonly reported systematic adverse reactions were fever (50 46%), fatig
15、ue (47 44%), headache (42 39%), and muscle pain (18 17%, Most adverse reactions that were reported in all dose groups were mild or moderate in severity. No serious adverse event was noted within 28 days post-vaccination. ELISA antibodies and neutralising antibodies increased significantly at day 14,
16、 and peaked 28 days post-vaccination. Specific T-cell response peaked at day 14 post-vaccination.Interpretation The Ad5 vectored COVID-19 vaccine is tolerable and immunogenic at 28 days post-vaccination. Humoral responses against SARS-CoV-2 peaked at day 28 post-vaccination in healthy adults, and ra
17、pid specific T-cell responses were noted from day 14 post-vaccination. Our findings suggest that the Ad5 vectored COVID-19 vaccine warrants further investigation.Funding National Key R&D Program of China, National Science and Technology Major Project, and CanSino Biologies.Copyright 2020 Elsevier Lt
18、d. All rights reserved.IntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in January, 2020. The virus is highly transmissible between humans and has spread rapidly, causing the COVID-19 pandemic户 Patients infected with SARS-CoV-2, especially older patients an
19、d those with pre-existing respiratory or cardiovascular conditions are at greater risk for severe complications, including severe pneumonia, acute respiratory distress syndrome, multiple organ failure, and in some cases, death.34 By May 20, 2020, SARS-CoV-2allowed access to the individual participan
20、t data. Proposals should be directed to jszfcvip.sina or cw0226foxmail . These proposals will be reviewed and approved by the sponsor, investigator, and collaborators on the basis of scientific merit. To gain access, data requesters will need to sign a data access agreement.AcknowledgmentsWe thank P
21、eng Deng, Qiong Li, and Xiaoai Qian from Hubei Provincial Center for Disease Control and Prevention for participant recruitment and sample collection. We thank Miao Xu and Jingjing Liu from the National Institute for Food and Drug Control (China), Yansong Sun, Sen Zhang, and Yuchang Li from the Beij
22、ing Institute of Microbiology and Epidemiology, and Feng Wang, Hongyan Hou, Hanxiong Guan, and Bo Liu from Tongji Hospital for laboratory analysis. We thank Ke Zhang from the Academy of Military Medical Sciences, Kun Liu from the General Hospital of Central Theater Command, and Changlong Fu from Wuh
23、an Rest Center, Chinese Peoples Armed Police Force for the management of the clinical trial site.ReferencesZhu N, Zhang D, Wang W, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med 2020; 382: 727-33.1 Li Q, Guan X, Wu P, et al. Early transmission dynamics in Wuhan,
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41、n SARS-CoV neutralizing antibody against epitope on S2 protein. Biochem Biophys Res Connmm 2005; 333:186-93.30 Wang Q, Zhang L, Kuwahara K, et al. Immunodominant SARS coronavirus epitopes in humans elicited both enhancing and neutralizing effects on infection in non-human primates. ACS Infect Dis 20
42、16; 2: 361-76.31 Gray GE, Moodie Z, Metch B, et al. Recombinant adenovirus type 5 HIV gag/pol/nef vaccine in South Africa: unblinded, long-term follow-up of the phase 2b HVTN 503/Phambili study.Lancet Infect Dis 2014; 14: 388-96.orProf Feng-Cai Zhu, NHC Key Laboratory of Enteric Pathogenic Microbiol
43、ogy, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Chinajszfcvip.sina Research in contextEvidence before this studyWe searched PubMed on May 8, 2020, for clinical trial reports with the terms XOVID-19 or SARS-CoV-2, vaccine”, and “clinical trial and no date or languag
44、e restrictions; no other data from a human clinical trial of COVID-19 vaccine have been reported thus far, to our knowledge. We also searched the ClinicalTrials.gov registry for unpublished trials of COVID-19 vaccines, up to May 6, 2020. In addition to the adenovirus type-5 (Ad5) vectored COVID-19 v
45、accine reported here, seven candidate COVID-19 vaccines are in ongoing clinical trials, including Modernas mRNA COVID-19 vaccine, Inovio Pharmaceuticals DNA vaccine, Sinovac, Wuhan and Beijing Institute of Biological Products inactive COVID-19 vaccines, University of Oxford/s chimpanzee adenovirus-v
46、ectored vaccine, and BioNTechs mRNA COVID-19 vaccine.Added value of this studyThis first-in-human trial showed that the Ad5 vectored COVID-19 vaccine was tolerable and immunogenic in healthy adults. One dose ofthe vaccine at all dose concentrations (5 x 1O10,1 x 1011, and 1*5 x 1011 viral particles)
47、 tested inducedstart clinical trials. These include Modernas mRNA COVID-19 vaccine and CanSinos non-replicating adenovirus type-5 (Ad5) vectored COVID-19 vaccine, which both entered phase 1 clinical trials on March 16, 2020; Inovio Pharmaceuticals DNA vaccine for COVID-19, which entered trials on Ap
48、ril 3, 2020; three inactive COVID-19 vaccines manufactured by Sinovac, Wuhan Institute of Biological Products, and Beijing Institute of Biological Products entered clinical trials in April, 2020, successively; University of Oxfords non-replicating chimpanzee adenovirus vectored vaccine ChAdOxl nCoV-19, and BioNTechs mRNA COVID-19 vaccine also started trials in recent months.Here, we report the preliminary assessment at 28 days post-vaccination of the safety, tolerability, and immunogenicity of CanSino/s non-replicating Ad5 vectored COVID-19 vaccine in healthy adults in