tetano
Editor, Senior Moderator
Lancet
. 2020 May 22;S0140-6736(20)31208-3.
doi: 10.1016/S0140-6736(20)31208-3. Online ahead of print.
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
Feng-Cai Zhu[SUP] 1 [/SUP], Yu-Hua Li[SUP] 2 [/SUP], Xu-Hua Guan[SUP] 3 [/SUP], Li-Hua Hou[SUP] 4 [/SUP], Wen-Juan Wang[SUP] 5 [/SUP], Jing-Xin Li[SUP] 5 [/SUP], Shi-Po Wu[SUP] 4 [/SUP], Bu-Sen Wang[SUP] 4 [/SUP], Zhao Wang[SUP] 3 [/SUP], Lei Wang[SUP] 3 [/SUP], Si-Yue Jia[SUP] 5 [/SUP], Hu-Dachuan Jiang[SUP] 5 [/SUP], Ling Wang[SUP] 2 [/SUP], Tao Jiang[SUP] 6 [/SUP], Yi Hu[SUP] 6 [/SUP], Jin-Bo Gou[SUP] 7 [/SUP], Sha-Bei Xu[SUP] 8 [/SUP], Jun-Jie Xu[SUP] 4 [/SUP], Xue-Wen Wang[SUP] 9 [/SUP], Wei Wang[SUP] 10 [/SUP], Wei Chen[SUP] 11 [/SUP]
Affiliations
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 ? 10[SUP]10[/SUP], 1 ? 10[SUP]11[/SUP], and 1?5 ? 10[SUP]11[/SUP] 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.
. 2020 May 22;S0140-6736(20)31208-3.
doi: 10.1016/S0140-6736(20)31208-3. Online ahead of print.
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
Feng-Cai Zhu[SUP] 1 [/SUP], Yu-Hua Li[SUP] 2 [/SUP], Xu-Hua Guan[SUP] 3 [/SUP], Li-Hua Hou[SUP] 4 [/SUP], Wen-Juan Wang[SUP] 5 [/SUP], Jing-Xin Li[SUP] 5 [/SUP], Shi-Po Wu[SUP] 4 [/SUP], Bu-Sen Wang[SUP] 4 [/SUP], Zhao Wang[SUP] 3 [/SUP], Lei Wang[SUP] 3 [/SUP], Si-Yue Jia[SUP] 5 [/SUP], Hu-Dachuan Jiang[SUP] 5 [/SUP], Ling Wang[SUP] 2 [/SUP], Tao Jiang[SUP] 6 [/SUP], Yi Hu[SUP] 6 [/SUP], Jin-Bo Gou[SUP] 7 [/SUP], Sha-Bei Xu[SUP] 8 [/SUP], Jun-Jie Xu[SUP] 4 [/SUP], Xue-Wen Wang[SUP] 9 [/SUP], Wei Wang[SUP] 10 [/SUP], Wei Chen[SUP] 11 [/SUP]
Affiliations
- PMID: 32450106
- DOI: 10.1016/S0140-6736(20)31208-3
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 ? 10[SUP]10[/SUP], 1 ? 10[SUP]11[/SUP], and 1?5 ? 10[SUP]11[/SUP] 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.