Journal Article

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

Guan, Xu-Hua, Gou, Jin-Bo, Wang, Wei, Wang, Wen-Juan, Xu, Jun-Jie, Wang, Xue-Wen, Wang, Bu-Sen, Jiang, Hu-Dachuan, Wu, Shi-Po, Li, Jing-Xin, Li, Yu-Hua, Jia, Si-Yue, Wang, Ling, Chen, Wei, Hu, Yi, Xu, Sha-Bei, Wang, Lei, Jiang, Tao, Wang, Zhao, Zhu, Feng-Cai, Hou, Li-Hua

2020

Overview

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. 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. 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. 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. National Key R&D Program of China, National Science and Technology Major Project, and CanSino Biologics.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Adenoviridae / Adenoviruses / Adolescent / Adult / Adults / Antibodies / Antibodies, Neutralizing - blood / Antibodies, Viral - blood / Betacoronavirus / Biological products / Blood / China / Clinical trials / Coronavirus Infections - prevention & control / Coronaviruses / COVID-19 / COVID-19 Vaccines / Cytometry / Deoxyribonucleic acid / Disease control / Disease prevention / DNA / Enzyme-Linked Immunosorbent Assay / Female / Fever / Glycoproteins / Headache / Humans / Immunity, Cellular / Immunity, Humoral / Immunization / Immunogenicity / Injection / Injections, Intramuscular / Laboratories / Lymphocytes T / Male / Middle Aged / Muscles / Muscular fatigue / Pain / Pandemics - prevention & control / Peptides / Pneumonia, Viral - prevention & control / Randomization / Safety / SARS-CoV-2 / Severe acute respiratory syndrome coronavirus 2 / Side effects / Spike glycoprotein / T-Lymphocytes - immunology / Vaccination / Vaccines / Vaccines, Synthetic - administration & dosage / Vaccines, Synthetic - adverse effects / Vaccines, Synthetic - therapeutic use / Viral diseases / Viral Vaccines - administration & dosage / Viral Vaccines - adverse effects / Viral Vaccines - therapeutic use / Viruses / Young Adult