First human trial of COVID-19 trial shows promising results
The first novel coronavirus (COVID-19) vaccine to reach phase 1 clinical trial has been found to be safe, well-tolerated, and able to generate an immune response against SARS-CoV-2 in humans, according to new research published in The Lancet.
The open-label trial in 108 healthy adults demonstrates promising results after 28 days, the final results will be evaluated in six months. Further trials are needed to tell whether the immune response it elicits effectively protects against SARS-CoV-2 infection.
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.
The new adenovirus type 5 vectored COVID-19 (Ad5-nCoV) vaccine evaluated in the trial is the first to be tested in humans. It uses a weakened common cold virus, adenovirus, which infects human cells readily but is incapable of causing disease, 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 COVID-19.
The trial assessed the safety and ability to generate an immune response of different dosages of the new Ad5-nCoV vaccine in 108 healthy adults between the ages of 18 and 60 years who did not have SARS-CoV-2 infection. Volunteers were enrolled from one site in Wuhan, China, and assigned to receive either a single intramuscular injection of the new Ad5 vaccine at a low, middle, or high dose.
The researchers tested the volunteers' blood at regular intervals following vaccination to see whether the vaccine stimulated both arms of the immune system, the body's humoral response, which produces neutralizing antibodies that can fight infection and could offer a level of immunity, and the body's cell-mediated arm, which depends on a group of T cells, rather than antibodies, to fight the virus. The ideal vaccine might generate both antibody and T cell responses to defend against SARS-CoV-2, the researchers said.
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 83 percent of those receiving low and middle doses of the vaccine and 75 percent in the high dose group reporting at least one adverse reaction within seven days of vaccination.
The 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 that can bind to COVIS-19 but do not necessarily attack it, and some participants had detectable neutralizing antibodies against SARS-CoV-2.
After 28 days, most participants had a four-fold increase in binding antibodies and half of participants in the low- and middle-dose groups and three-quarters of those in the high-dose group showed neutralizing antibodies against SARS-CoV-2.
The researchers said the Ad5-nCoV vaccine also stimulated a rapid T cell response in many participants, which was greater in those given the higher and middle doses of vaccine. Further analyses showed that 28 days after vaccination, the majority of recipients showed either a positive T cell response or had detectable neutralizing antibodies against SARS-CoV-2.
However, the authors note that both the antibody and T-cell response could be reduced by high pre-existing immunity to adenovirus type 5, the common cold virus vector and carrier. In the study, 44-56 percent of participants in the trial had high pre-existing immunity to adenovirus type 5, and had a less positive antibody and T-cell response to the vaccine.
"These results represent an important milestone,” said Wei Chen, PhD, lead author of the study, from the Beijing Institute of Biotechnology in Beijing, China. “The trial demonstrates that a single dose of the Ad5-nCoV vaccine produces virus-specific antibodies and T cells in 14 days, making it a potential candidate for further investigation. However, these results 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.”