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
Main result
At least one adverse reaction in the first 7 days after vaccination was reported in 30 (83%) participants in the low-dose group, 30 (83%) participants in the medium-dose group and 27 (75%) participants in the high-dose group. Most of the undesirable effects reported were of mild to moderate intensity: pain at the injection site was present in 58 (54%) of the vaccinated, fever in 50 vaccinated (46%), fatigue in 47 participants (44%), headache in 42 vaccinated (39%) and muscle pain in 18 participants (17%).
No serious adverse events
ELISA and neutralizing antibodies increased significantly on D14 and peaked on D28. The specific T-cell response peaked on D14.
Takeaways
The vaccine in high doses tended to be more immunogenic than medium and low dose vaccines. It was also associated with higher reactogenicity. Severe fever, fatigue, dyspnea, muscle pain, and joint pain have been reported in some of the recipients in the high-dose group.
Strength of evidence Weak
Monocentric, non-randomized, open, phase 1 trial; Intention-to-treat analysis; n = 108
Preliminary study, with a follow-up during the first 28 days
Realization of the study in a "rehabilitation center"?
Self-report of adverse reactions within 28 days, with investigator verification during the first 14 days
About half of the participants in the 3 groups had a pre-existing titer of Ad5 neutralizing antibody (> 1: 200).
No participant was over 60 and only 17 participants were over 50 (16%)
Forty participants after vaccination, given the active circulation of the virus in Wuhan
Objectives
Method
Monocentric, open, non-randomized, phase 1 therapeutic trial (in Wuhan).
Preliminary evaluation after 28 days in healthy elderly adults (negative serology and negative chest CT scan) from 18 to 60 years, included sequentially (first low dose, waiting at least 3 days after injections, then recruitment of the medium-dose group, etc.). Three dose groups (5 × 10¹⁰ viral particles for 0.5 mL, 1 × 10¹¹ for 1 mL and 1.5 × 10¹¹ for 1.5 mL) by intramuscular (IM) injection. Inclusion between March 16 and March 27.
Exclusion criteria: a history of convulsions or mental illness, allergy to any ingredient included in the vaccine, acute febrile illness on the day of registration, treatment with a blood product in the last 4 months, vaccination or medication as part of research in the past month, inability to meet study schedule.
The primary outcome measure was the occurrence of adverse events within 7 days of vaccination.
Safety was assessed 28 days after vaccination. Specific antibodies were measured by ELISA and the neutralizing antibody responses induced by the vaccination were detected with tests for neutralization of the SARS-CoV-2 virus and for neutralization of pseudoviruses. T-cell responses were assessed by enzyme-linked immunospot and flow cytometry tests. The results were considered positive if there was at least a double increase in the number of T cells secreting IFNy after vaccination.
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