Promising results for first human trial of COVID-19 vaccine
The first 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 a study published in The Lancet.
The COVID-19 vaccine — the first to be tested in humans — 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 recognise that spike protein and fight off the coronavirus.
The open-label trial assessed the safety and ability to generate an immune response of different dosages of the adenovirus type 5 vectored COVID-19 (Ad5-nCoV) vaccine in 108 healthy adults between the ages of 18 and 60 years. Volunteers were enrolled from one site in Wuhan and assigned to receive either a single intramuscular injection of the new Ad5 vaccine at a low dose (5 x 1010 viral particles/0.5 mL), middle dose (1 x 1011 viral particles/1 mL) or high dose (1.5 x 1011 viral particles/1.5 mL).
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% of those receiving low and middle doses of the vaccine and 75% 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 reported in 54% of vaccine recipients, fever (46%), fatigue (44%), headache (39%) and muscle pain (17%). 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.
The researchers also tested the volunteers’ blood at regular intervals to see whether the vaccine stimulated both arms of the immune system: the body’s ‘humoral response’ (the part of the immune system that produces neutralising antibodies which 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.
Within two weeks of vaccination, all dose levels of the vaccine triggered some level of immune response in the form of binding antibodies (which can bind to the coronavirus but do not necessarily attack it) — these were found in 44% of the low-dose group, 50% of the medium-dose group and 61% of the high-dose group. Some participants also had detectable neutralising antibodies against SARS-CoV-2 — 28% of the low-dose group, 31% of the medium-dose group and 42% of the high-dose group. After 28 days, most participants had a four-fold increase in binding antibodies (97% of the low-dose group, 94% of the middle-dose group and 100% of the high-dose group), and half of participants in the low- and middle-dose groups and three-quarters of the high-dose group showed neutralising antibodies against SARS-CoV-2.
Importantly, the Ad5-nCoV vaccine also stimulated a rapid T cell response in the majority of volunteers, with levels peaking at 14 days after vaccination (83.3% of the low-dose group and 97.2% of the medium- and high-dose groups). Further analysis showed that 28 days after vaccination, the majority of recipients showed either a positive T cell response or had detectable neutralising antibodies against SARS-CoV-2 (78% of the low-dose group, 92% of the medium-dose group and 100% of the high-dose group).
However, the authors noted 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/carrier) — in the study, 44-56% 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.
“Our study found that pre-existing Ad5 immunity could slow down the rapid immune responses to SARS-CoV-2 and also lower the peaking level of the responses,” said Professor Feng-Cai Zhu from Jiangsu Provincial Center for Disease Control and Prevention, who led the study. “Moreover, high pre-existing Ad5 immunity may also have a negative impact on the persistence of the vaccine-elicited immune responses.”
A randomised, double-blinded, placebo-controlled phase 2 trial of the Ad5-nCoV vaccine has now been initiated in Wuhan to determine whether the results can be replicated, and if there are any adverse events up to six months after vaccination, in 500 healthy adults — 250 volunteers given a middle dose, 125 given a low dose and 125 given a placebo as a control. This will include participants over 60 years old — an important target population for the vaccine.
“The trial demonstrates that a single dose of the new adenovirus type 5 vectored COVID-19 (Ad5-nCoV) vaccine produces virus-specific antibodies and T cells in 14 days, making it a potential candidate for further investigation,” said Professor Wei Chen from the Beijing Institute of Biotechnology, who is responsible for the study.
“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.”
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