- Early-stage clinical trials show that three COVID-19 vaccines are generally safe and induce an immune response in healthy people.
- The results of two of these studies were published online yesterday in The Lancet. One is a phase 1 and 2 trial by researchers at
Oxford Universitywith support from AstraZeneca.
- The other is a phase 2 trial by Chinese researchers supported by
Three more COVID-19 investigational vaccines have been shown in early clinical trials to be generally safe and to induce an immune response in healthy volunteers.
The results of two of these studies were published online yesterday in The Lancet. One is a phase 1 and 2 trial by researchers at
The third is a phase 1 and 2 study by U.S. pharmaceutical company Pfizer and German biotechnology company BioNTech. These results were published yesterday to the online preprint server medRxiv.org and have not yet been published in a peer-reviewed journal.
Deborah Fuller, PhD, a professor of microbiology at the University of Washington School of Medicine in Seattle, who was not involved in these studies, said the results are “promising,” but more research is needed.
“Both groups saw the immune responses that they were hoping to see,” she said, “and the adverse effects weren’t severe enough to keep them from moving forward.”
“What those levels of immune responses mean, in terms of protection from SARS-CoV-2 [the coronavirus that causes COVID-19], we’re not going to learn until they do the phase 3 trials,” she added.
The Oxford candidate vaccine induced an antibody immune response within 28 days after vaccination and a T-cell immune response within 14 days after vaccination.
These were still present 56 days after vaccination. Researchers will continue monitoring participants for at least 1 year to see how long the immune responses last.
Neutralizing antibodies — at a level that could potentially neutralize the virus — were detected in most people after one dose of the vaccine and in all who had a second booster dose 28 days after the first.
Only 10 people received the second dose.
Although neutralizing antibodies have been found in the plasma of people who have recovered from COVID-19, scientists don’t yet know what level of antibodies will protect people against the new coronavirus.
However, Fuller says the induction of both kinds of immune responses specific for the new coronavirus is a good sign.
“There’s increasing evidence to suggest that T-cell responses may play an important role in protection from SARS-CoV-2,” she said.
Antibodies prime the immune system to target viruses and other invaders in the blood or lymphatic system. T cells are part of the cellular immune response and help the immune system attack infected cells.
“T cells are like a backup plan,” said Fuller. “If you don’t have sufficient antibodies to block the infection, T cells would come in and find infected cells, and eliminate them quickly.”
The vaccine trial included 1,077 healthy adults aged 18 to 55 years from the United Kingdom. None of them had a history of infection with SARS-CoV-2. About half were female and over 90 percent were white.
Given the limited range of people included in the trial, it’s not clear how well the vaccine would perform in older adults, people with other health conditions, or ethnically and geographically diverse populations.
Mild or moderate side effects were fairly common among people given the vaccine, with fatigue or headache the most frequent. Other common side effects included pain at the injection site, muscle ache, chills, and high temperature.
Certain side effects were reduced in people who took a pain reliever before and for 24 hours after their vaccination. Side effects were also less common in people after the second dose of the vaccine.
Researchers have already begun phase 3 trials of the candidate vaccine in Brazil, South Africa, and the United Kingdom.
AstraZeneca says it has the capacity to produce 2 billion doses of the vaccine should it prove effective in later clinical trials, reports CNN.
There are 24 COVID-19 candidate vaccines in clinical trials around the world, with another 141 at earlier stages of development,
The phase 2 trial of the CanSino candidate vaccine showed that it was generally safe and induced an immune response.
The vaccine trial, conducted in Wuhan, China, included 508 healthy adults up to 83 years. People had not previously had COVID-19.
Researchers randomly assigned people to receive either a high or low dose of the candidate vaccine, or an inactive placebo.
Fewer people developed neutralizing antibodies than in the Oxford study — 59 percent of the high-dose group and 47 percent of the low-dose group.
However, the candidate vaccine induced a T-cell response in 90 percent of the high-dose group and 88 percent of the low-dose group.
Both types of immune responses were present at 28 days.
This vaccine uses a weakened human common cold virus (adenovirus) to deliver the genetic code for the new coronavirus’ spike protein to the body’s cells.
The cells then produce the spike protein, which teaches the immune system to recognize that protein and fight the new coronavirus.
Fuller says many people in the world have already been exposed to the common cold virus, so they have some immune protection to it. This could interfere with the immune response generated by a vaccine that uses the adenovirus as a delivery system.
Chinese researchers saw this kind of blunted immune response in people who had pre-exi
sting immunity to the adenovirus.
The Oxford vaccine also uses an adenovirus to deliver the new coronavirus’ genetic code, but it is a chimp adenovirus, so it should be less of a concern, says Fuller.
“We haven’t been exposed to that adenovirus yet,” she said, “so it should have the potential to induce full immune responses.”
The antibody response with the CanSino candidate vaccine was also lower in people 55 years or older. This is concerning because this age group is at
Most adverse reactions for this candidate vaccine were mild or moderate. However, 9 percent of people in the high-dose group had a severe adverse reaction, with fever as the most common.
In an accompanying commentary
However, “Much remains unknown about these and other COVID-19 vaccines in development,” they added, “including longevity of response and [immune responses] in older adults or other specific groups, such as those with comorbidities who are often excluded from clinical trials, or ethnic or racial groups more severely affected by COVID-19.”
Some of these answers will come from phase 3 clinical trials. In these larger studies, researchers will follow people who are vaccinated to see if they are exposed to the new coronavirus or develop COVID-19.
These studies, though, will need to include a more diverse group of volunteers.
“That’s something that needs to be done in the next set of studies, to really look at whether or not you’re going to be able to immunize these [other] populations,” said Fuller of the Oxford vaccine. “Or is this going to be a vaccine that’s restricted to the healthy and the young?”