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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 06 13; 395(10240):1845-1854.Lct

Abstract

BACKGROUND

A vaccine to protect against COVID-19 is urgently needed. We aimed to assess 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, 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 (5 × 1010, 1 × 1011, and 1·5 × 1011 viral particles) to receive an intramuscular injection of vaccine. The primary outcome 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. T-cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays. This study is registered with ClinicalTrials.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 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 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%]), fatigue (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, 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 rapid 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 Biologics.

Authors+Show Affiliations

NHC Key Laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China. Electronic address: jszfc@vip.sina.com.China National Institute for Food and Drug Control, Beijing, China.Hubei Provincial Center for Disease Control and Prevention, Wuhan, China.Beijing Institute of Biotechnology, Beijing, China.NHC Key Laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China.NHC Key Laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China.Beijing Institute of Biotechnology, Beijing, China.Beijing Institute of Biotechnology, Beijing, China.Hubei Provincial Center for Disease Control and Prevention, Wuhan, China.Hubei Provincial Center for Disease Control and Prevention, Wuhan, China.NHC Key Laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China.NHC Key Laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China.China National Institute for Food and Drug Control, Beijing, China.Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing, China.Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing, China.CanSino Biologics, Tianjin, China.Clinical Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.Beijing Institute of Biotechnology, Beijing, China.Shanghai Canming Medical Technology, Shanghai, China.Clinical Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: wwang@vip.126.com.Beijing Institute of Biotechnology, Beijing, China. Electronic address: cw0226@foxmail.com.

Pub Type(s)

Clinical Trial, Phase I
Journal Article

Language

eng

PubMed ID

32450106

Citation

Zhu, Feng-Cai, 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 (London, England), vol. 395, no. 10240, 2020, pp. 1845-1854.
Zhu FC, Li YH, Guan XH, 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.
Zhu, F. C., Li, Y. H., Guan, X. H., Hou, L. H., Wang, W. J., Li, J. X., Wu, S. P., Wang, B. S., Wang, Z., Wang, L., Jia, S. Y., Jiang, H. D., Wang, L., Jiang, T., Hu, Y., Gou, J. B., Xu, S. B., Xu, J. J., Wang, X. W., ... Chen, W. (2020). 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 (London, England), 395(10240), 1845-1854. https://doi.org/10.1016/S0140-6736(20)31208-3
Zhu FC, 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 06 13;395(10240):1845-1854. PubMed PMID: 32450106.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Zhu,Feng-Cai, AU - Li,Yu-Hua, AU - Guan,Xu-Hua, AU - Hou,Li-Hua, AU - Wang,Wen-Juan, AU - Li,Jing-Xin, AU - Wu,Shi-Po, AU - Wang,Bu-Sen, AU - Wang,Zhao, AU - Wang,Lei, AU - Jia,Si-Yue, AU - Jiang,Hu-Dachuan, AU - Wang,Ling, AU - Jiang,Tao, AU - Hu,Yi, AU - Gou,Jin-Bo, AU - Xu,Sha-Bei, AU - Xu,Jun-Jie, AU - Wang,Xue-Wen, AU - Wang,Wei, AU - Chen,Wei, Y1 - 2020/05/22/ PY - 2020/05/08/received PY - 2020/05/18/revised PY - 2020/05/18/accepted PY - 2020/5/26/pubmed PY - 2020/6/18/medline PY - 2020/5/26/entrez SP - 1845 EP - 1854 JF - Lancet (London, England) JO - Lancet VL - 395 IS - 10240 N2 - BACKGROUND: A vaccine to protect against COVID-19 is urgently needed. We aimed to assess 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, 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 (5 × 1010, 1 × 1011, and 1·5 × 1011 viral particles) to receive an intramuscular injection of vaccine. The primary outcome 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. T-cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays. This study is registered with ClinicalTrials.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 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 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%]), fatigue (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, 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 rapid 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 Biologics. SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/32450106/full_citation L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(20)31208-3 DB - PRIME DP - Unbound Medicine ER -