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
Fecha
2020Autor
Zhu, Feng-Cai
Li, Yu-Hua
Guan, Xu-Hua
Hou, Li-Hua
Wang, Wen-Juan
Li, Jing-Xin
Wu, Shi-Po
Wang, Bu-Sen
Wang, Zhao
Wang, Lei
Jia, Si-Yue
Jiang, Hu-Dachuan
Wang, Ling
Jiang, Tao
Hu, Yi
Gou, Jin-Bo
Xu, Sha-Bei
Xu, Jun-Jie
Wang, Xue-Wen
Wang, Wei
Chen, Wei
Imagenes y Videos
Resumen
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.
Palabras clave
COVID-19; VaccineEnlace al recurso
https://doi.org/10.1016/Colecciones
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