Phase 1 Results
A review and summary of the Phase 1 trial for this vaccine can be found here.
Randomized Controlled Trial
Study population and setting
This study was a phase 2 clinical trial including 508 healthy adults from Wuhan, China age 18 and older. Low (5×10^10 viral particles) and medium (1×10^11 viral particles) doses from the phase 1 trial were selected for the study, as well as a placebo group, and randomized in a 2:1:1 fashion, respectively. Blood samples were collected on days 0, 14, and 28. Samples were tested for immunogenicity and patients were monitored to determine vaccine safety profiles.
Summary of Main Findings
Both vaccine doses resulted in SARS-CoV-2 RBD specific antibody responses by day 14, with even higher titers by day 28. Both doses also resulted in neutralizing antibody responses to live virus, as well as IFN-gamma T-cell responses. Participants age 55 years and older had a less immunogenic response to the vaccine, and many of them also had higher pre-existing adenoviral immunity. Both age and pre-existing Ad5 immunity could partially hamper immune response to the vaccine, and therefore these groups might be better suited for a booster dose of vaccine. This will be further explored in a phase 2b trial. The most common adverse events reported were fatigue, fever, and headache, as well as pain at injection site. Overall, the 5×10^10 viral particle dose group had a better safety profile with a comparable immune response to the 1×10^11 viral particle dose group.
This was the first phase 2 trial for the non-replicating Ad5-vectored COVID-19 vaccine. This vaccine trial included a placebo group, and it had a wide range of ages in the participant pool, including a considerable percentage (13%) age 55 and older. This allowed them to analyze differences in vaccine response in the vulnerable older population. The vaccine did show promising results by inducing seroconversion and neutralizing antibodies, as well as positive T-cell responses.
One limitation of this trial was that they began the phase 2 trial before the complete results of the phase 1 trial were available, therefore making the investigators unable to perform power calculations for this trial based on their previous results. This also caused them to make assumptions as to which vaccine dose would perform best, assigning more participants to that group, which turned out to be inaccurate. Next, all participants were from Wuhan, China, and no children were included in the study. Pre-existing Ad5 immunity is highly prevalent in the global population, and therefore there will likely be a large amount of pre-existing immunogenicity to the vaccine construct, which could dampen its effectiveness. Data was also only collected up to 28 days post-vaccination, and therefore long-lasting immunity is still in question. Additionally, the correlates of protection against SARS-CoV-2 are still unknown. Finally, the researchers did not compare their results to those found in convalescent plasma, which has been used in other studies as a comparison group.
First report of results from the Ad5-vectored COVID-19 vaccine phase 2 trial, with promising findings warranting proceeding to phase 3 trials.
This review was posted on: 26 July 2020