Can the safety of a vaccine be established in large enough numbers within the next four to five months?
This is the plan of the Oxford University team who are working at unprecedented speed to develop a vaccine against COVID-19.
By September, all going well, the Oxford scientists will begin jabbing a million arms with their new vaccine called ChAdOx1 nCoV-19.
Does it work? We may know in a few weeks
Three days ago, Sir John Bell, the Regius Professor of Medicine at Oxford University, told NBC that the researchers would likely know if the their vaccine actually works by the beginning of June.
Professor Bell said the chances of success were “pretty good.”
He said, “We are gradually reeling it in, bit by bit and as every day goes by, the likelihood of success goes up.”
Professor Bell said it appeared that the vaccine would probably need to be given seasonally, along the lines if the influenza vaccine.
We could be getting jabbed every year
“Coronavirus doesn’t mutate at the pace of flu as far as we can see but it’s also quite a tricky virus in terms of dictating long-term immune responses to it and as a result I suspect we may need to have relatively regular vaccinations against coronavirus going into the future. That of course remains to be see,” Professor Bell said.
My bet at the moment is that this is likely to be a seasonal coronavirus vaccine.”
Safety of the vaccine, however, remains the big question.
“I think we’ve got reason to believe that the efficacy, the efficacy of the vaccine in terms of generating strong antibody responses is probably going to be OK. The real question is whether the safety profile’s going to be fine. So that’s actually the main focus of the clinical studies,” he said.
Can the vaccine’s safety be established by September?
As The New Daily reported two weeks ago, when the first clinical trials began, those million doses were reportedly already being manufactured without the safety and efficacy of the vaccine being proved.
“We have started at-risk manufacturing of this vaccine not just on a smallish scale… but with a network of manufacturers in as many as seven different places around the world,” Professor Adrian Hill, Director of the Jenner Institute at Oxford University, said last month in an online news briefing.
The aim is to have at least a million doses by around about September.”
The Phase II trial underway involves about 1000 volunteers. It will prove to be safe in a relatively small number of people or not. All going well, the plan is then move quickly to a Phase III trial of about 5000 volunteers.
Volunteer group on the lower end of the scale
Dr Gaetan Burgio is a group leader in the Department of Immunology and Infectious Disease at the John Curtin School of Medical Research.
Dr Burgio told The New Daily that Phase III trials “usually involves a large population… For example for anti-malarial close to 10,000 patients are usually enrolled for such trial.”
He said that a study of 5000 “seems to be in the lower end” but it might be enough to show a protective effect of the vaccine against SARSCov2.
Indeed, Phase III trials have involved as few as 3000 volunteers or even less. So, the Oxford trial fits within the normal testing parameters.
But there are other factors that give researchers confidence in the Oxford trial and other similar projects.
Previous work with coronaviruses
“These vaccines largely build up on the previous vaccine candidates that have been designed for MERS or SARS five to 10 years ago due to the similarity of these viruses with SARS-Cov2,” said Dr Burgio.
“This is the case for the Oxford vaccine and this is a good news for the rapid development of a vaccine for COVID19.”
How much time do the researchers need to wait for a negative reaction in order to give the vaccine an all-clear?
Dr Burgio said the side effects could be immediate such as an immediate response to the adenovirus (the envelop, or carrying agent, of the vaccine) such as flu-like symptoms or others symptoms due to an immediate reaction to the vaccine.
“Other reactions would take several weeks such as an immune reaction to the vaccine,” he said.
Usually the waiting time for rare side effects is around couple of weeks.
“These rare side effects are predominantly due to an over reaction to the vaccine. However, it is a real challenge to distinguish these side effects from the long term effect of the virus, another infection or a sickness.”
While Dr Burgio expressed doubt that a million doses could be manufactured in such a short period of time, he suggested their deployment would be in a Phase IV trial, which normally requires regulatory approval.
No straightforward template
Professor Kristine Macartney is a paediatrician specialising in infectious diseases and vaccinology. Kristine is currently the Director of the National Centre for Immunisation Research and Surveillance (NCIRS).
Professor Macartney said that 5000 volunteers for an effective Phase III trial “sounds about right” in terms of establishing safety, but she noted that every COVID-19 vaccine under development (about 100 across the world) would require “a tailored safety plan.”
In other words, there is no straightforward template to work off.
She also made the point that generating an immune response is not the same thing as having a vaccine that is effective in preventing the disease.
The challenge will still be for every single vaccine to jump through various gates and hoops,” Professor Macartney said.
“Are these candidate vaccines generating an immune response, what type of immune response are they generating (antibodies or T-calls), are they safe, which is critical, and do they prevent the disease?”
She also noted that “in parallel, across the globe, the scientific community is still learning what type of immune response that infected people develop.”
Within just a few weeks, we might know if the Oxford crew has through sheer boldness, and clever study design, cracked the code and shed light on these vital known unknowns.