First Human Trial of SARS-CoV-2 Vaccine: Initial Results In
Researchers from China report the initial findings of the first human trial for a potential vaccine against SARS-CoV-2, the new coronavirus. The results are promising, suggesting that the vaccine is mostly safe and apparently effective.
At present, there are numerous clinical trials around the world testing potential vaccines against the new coronavirus, SARS-CoV-2.
The first human trial for such a vaccine started in early March. It is the work of researchers from several Chinese institutions, including the China National Institute for Food and Drug Control in Beijing, the Beijing Institute of Biotechnology, and the Chinese vaccine company CanSino Biologics.
Phase 1 of this trial, which tests primarily for safety, has recently concluded, and the scientists now report their findings in The Lancet.
Thus far, the team is satisfied that the vaccine they are testing is mostly safe and holds the promise of effectiveness.
“These results represent an important milestone,” says lead researcher Prof. Wei Chen, from the Beijing Institute of Biotechnology in Beijing.
What Type of Vaccine Is It?
The vaccine in this clinical trial is called the “adenovirus type 5 vectored COVID-19 (Ad5-nCoV) vaccine.”
The vaccine uses an adenovirus — a common virus — that is no longer able to replicate or infect — as the “base” to which spike proteins specific to SARS-CoV-2 are attached.
Spike proteins are proteins present on the surface of viruses, which “help” the virus to infect healthy cells and spread further.
By using an inactivated virus that features the SARS-CoV-2-specific spike protein, the vaccine’s purpose is to “teach” the human immune system to recognize the presence of SARS-CoV-2 and fight the virus.
In phase 1, the researchers recruited 108 participants, of whom 51% were male and 49% female, with a mean age of 36.3 years.
The researchers split the participants into three equal groups to test three dosages of the vaccines: a low dose, a middle dose, and a high dose.
This trial was not randomized, and it was open-label, meaning that the researchers knew what they were administering, and the participants knew what they were receiving.
Well Tolerated with Mild Adverse Reactions
The researchers collected and assessed blood samples from the participants regularly after the vaccinations. They also kept track of any emerging symptoms the participants might experience.
At the 28-day mark post vaccination, the results indicated that the participants tolerated the experimental vaccine well, and, while many volunteers did have adverse reactions, these were not serious and did not last long.
Of the participants who received a low dose of the vaccine, 30 (83%) reported at least one adverse reaction within 7 days from inoculation. The same proportion who received the middle dose reported adverse reactions within the same time frame.
Of those who received a high dose of the vaccine, 27 (75%) reported at least one adverse reaction within a week of vaccination.
The researchers note that the most common reactions were pain where they had received the injection (58 participants), fever (50 participants), a sense of fatigue (47 participants), headaches (42 participants), and muscle pain (18 participants).
Only one participant — who received a high dose of the vaccine — experienced “severe fever […] with axillary temperature greater than 38.5 [degrees Celsius],” as well as severe fatigue, shortness of breath, and muscle pain. These symptoms subsided within 48 hours.
Two participants who received a low dose of the vaccine, two who received a middle dose, and five who had a high dose reported episodes of severe fever, too, but none of the other symptoms.
Is It Likely to be Effective?
While this phase 1 clinical trial did not test for effectiveness by analyzing blood samples, the researchers were able to see if the vaccine had triggered an immune system reaction, a preliminary indicator that the vaccine is doing its job.
The researchers report that 14 days after the inoculation, all the participants, regardless of which dose they had, saw a rise in binding antibodies, molecules that “recognize” and attach to the virus, though they do not fight it.
Some of the participants, however, also presented neutralizing antibodies — or ones that do fight the virus — at 14 days after inoculation.
Specifically, 10 of the participants who had received low doses of the vaccine, 11 on a medium dose, and 15 of those who had high doses had a fourfold increase in neutralizing antibodies against SARS-CoV-2.
However, a rise in neutralizing antibodies “peaked” at 28 days post-vaccination. Eighteen of the participants on the low dose group, 18 of those in the middle dose group, and 27 of those from the high dose group presented neutralizing antibodies at that point.
But the researchers were most interested in whether or not the experimental vaccine would quickly induce the key immune cells known as T cells to respond.
“The trial demonstrates that a single dose of the new [Ad5-nCoV] vaccine produces virus-specific antibodies and T cells in 14 days, making it a potential candidate for further investigation,” notes Prof. Chen.
The researchers found activity from two types of T cells — CD4+ and CD8+ — both at 14 days and at 28 days after vaccination, in participants from all dose groups.
Those who received a high dose of the experimental vaccine had a higher expression of cytokines (special proteins) that both types of T cells secrete than those in the low and middle dose groups.
“However,” Prof. Chen warns, “these results should be interpreted cautiously.”
Going forward, the researchers have started phase 2 of the clinical trial, which aims to replicate the current results and find out whether participants experience any adverse effects at 6 months after inoculation.
Moreover, the team aims to recruit participants aged 60 years and over for phase 2 of this trial to find out whether the vaccine can protect the demographic with a higher risk of developing COVID-19, the disease that SARS-CoV-2 causes.