Open-label trial of new Ad5 vectored COVID-19 vaccine found to be safe, well-tolerated, and able to generate an immune response against SARS-CoV-2 in humans.
The creation of an effective vaccine is seen as the long-term solution to controlling the COVID-19 pandemic. Currently there are more than 100 candidate COVID-19 vaccines in development worldwide.
Published in The Lancet in May 2020, the first COVID-19 vaccine to reach Phase I of a clinical trial has been found to be safe, well-tolerated and able to generate an immune response against SARS-CoV-2 in humans.
The study was funded by National Key R&D Program of China, National Science and Technology Major Project, and CanSino Biologic. Researchers from institutions across China came together for this trial.
Through the Phase I clinical trial, researchers were able to demonstrate safety and ability of the new adenovirus type 5 vectored COVID-19 (Ad5-nCoV) vaccine in generating an immune response. The trial recruited 108 healthy adults between the ages of 18 and 60 years who did not have SARS-CoV-2 infection.
The new Ad5-nCoV vaccine evaluated in this trial is the first to be tested in humans. It uses a weakened common cold virus to deliver genetic material that codes for the SARS-CoV-2 spike protein to the cells. These cells then produce the spike protein, and travel to the lymph nodes where the immune system creates antibodies that will recognize that spike protein and fight off the coronavirus.
Volunteers were enrolled from one site in Wuhan, China, and assigned to receive either a single intramuscular injection of the new Ad5-nCoV vaccine at a low dose (5 × 1010 viral particles/0·5ml, 36 adults), middle dose (1×1011 viral particles/1.0ml, 36 adults), or high dose (1.5 x 1011 viral particles/1.5ml, 36 adults).
Upon blood testing of the volunteers at regular intervals, researchers found that the vaccine candidate was well-tolerated at all doses with no serious adverse events reported within 28 days of vaccination. Most adverse events were mild or moderate with at least one adverse reaction in the high dose group within seven days of vaccination.
Most common adverse reactions were mild pain at the injection site, fever, fatigue, headache, and muscle pain. One participant given the higher dose vaccine reported severe fever along with severe symptoms of fatigue, shortness of breath, and muscle pain--however these adverse reactions persisted for less than 48 hours.
Within two weeks of vaccination, all dose levels of the vaccine triggered some level of immune response in the form of binding antibodies, and some participants had detectable neutralising antibodies against SARS-CoV-2.
After 28 days, most participants had a four-fold increase in binding antibodies, with those in the high-dose group showing neutralising antibodies against SARS-CoV-2. The new vaccine also found to stimulate a rapid T-cell response in majority of volunteers.
The authors however, cautioned that the antibody and T-cell response could be reduced by high pre-existing immunity to adenovirus type 5. Also, with the small sample size, relatively short duration and lack of randomisation this could limit the ability of the trial in picking up any more adverse reactions to the vaccine.
Professor Wei Chen from the Beijing Institute of Biotechnology in Beijing, China, who is responsible for the study explained that the results of the trial should be interpreted cautiously.
“The challenges in the development of a COVD-19 vaccine are unprecedented, and the ability to trigger these immune responses does not necessarily indicate that the vaccine will protect humans from COVID-19. This result shows a promising vision for the development of COVID-19 vaccines, but we are still a long way from this vaccine being available to all."
The vaccine will be moving on to a randomised, double-blinded, placebo-controlled phase II trial in Wuhan, China to determine whether the results can be replicated, and if there are any adverse events up to six months after vaccination.