Results of Phase 1 Trial of Recombinant Adenovirus type-5 Vectored COVID-19 Vaccine

A team of investigators report on the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored vaccine for COVID-19.

A recombinant adenovirus type-5 (Ad5)-vectored COVID-19 vaccine expressing the spike glycoprotein of SARS-CoV-2 was deemed tolerable and immunogenic at 28 days following vaccination. According to the data published in The Lancet, this Ad5-vectored COVID-19 vaccine warrants further investigation.

To assess the safety, tolerability and immunogenicity of this vaccine, investigators performed a dose-escalation, single-center, open-label, nonrandomized phase 1 trial in Wuhan, China ( Identifier: NCT04313127). In total, 108 adults between age 18 and 60 years were recruited (51% men, 49% women, and mean age 36.3 years). Participants were divided into 3 groups of 36 and received either a low, middle, or high dose of the vaccine.

At least 1 adverse reaction was reported in 83% of individuals in the middle- and low-dose groups and in 75% of individuals in the high-dose groups within the first 7 days following vaccination. Pain was the most common injection site adverse reaction and was reported in 54% of all participants. The most commonly reported systemic adverse reactions were fever (46%), fatigue (44%), headache (39%), and muscle pain (17%). Most reactions were mild or moderate in severity, and there was no serious adverse event noted within 28 days following vaccination.

At day 14, enzyme-linked immunosorbent assay (ELISA) antibodies and neutralizing antibodies increased significantly and peaked 28 days following vaccination. The specific T-cell response peaked at day 14 following vaccination.

It must be noted that the study was limited by small cohort size, short duration of follow-up, and the lack of a randomized control group. The study was also not designed to measure vaccine efficacy; rather the goal was to evaluate safety and tolerability in healthy adults with no interference by underlying diseases or medicines. However, the investigators do report unpublished data claiming that 7 of 8 ferrets in preclinical studies were protected from having detectable virus when challenged through nasal dripping 21 days after immunization compared with 1 of 8 in the control group.

According to the investigators, “results of our study indicated that older age could have a negative effect on the vaccine-elicited responses to SARS-CoV-2”; however, no participants in the trial were older than age 60 and only 16% we

re older than 50, providing little information on the capability of generating a potent cellular and humoral response in the older population.

The investigators conclude that the Ad5-vectored COVID-19 vaccine is tolerable and immunogenic in health adults, adding, “there is potential for further investigation of

the Ad5 vectored COVID-19 vaccine for the control of the COVID-19 outbreak.” An ongoing phase 2 trial ( Identifier: NCT04341389) is set to provide more information.


Zhu F-C, Li Y-H, Guan X-H, et al. 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. Lancet. 2020; 395:1845-1854.