Interventional study with open label/non-randomised methodology
In this paper, just published in Lancet, the authors performed a dose-escalation, single-centre, open-label, non-randomised, phase 1 trial of a recombinant adenovirus type-5 (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 enzyme-linked immunosorbent assay (ELISA), and 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. 108 participants (51% male, 49% female; mean age 36·3 years) were recruited and received low dose (n=36), middle dose (n=36), or high dose (n=36) vaccine. 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 reported in all dose groups were either mild or moderate in severity. No serious adverse events were 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 authors concluded that Ad5 vectored COVID-19 vaccine is tolerable and immunogenic at 28 days post-vaccination suggesting that the Ad5 vectored COVID-19 vaccine warrants further investigation.