The University of Oxford has resumed its late-stage clinical trial in the United Kingdom of a COVID-19 vaccine candidate among 10,000 participants that was halted last week due to a volunteer recipient suffering an unexplained illness.
The Oxford University-AstraZeneca vaccine is seen as a strong contender to win the race to produce a vaccine among dozens of efforts globally.
The university is developing the vaccine in partnership with AstraZeneca, and is testing it on thousands of people in the UK (phase II-III), Brazil (phase II-III), and South Africa (phase I-II). Further trials are planned in Japan and Russia. Across these five countries 20,000 participants will be tested.
A trial in the US that is due to recruit 30,000 participants at 80 sites, making it the largest single testbed for the vaccine, has remained halted since 6 September due to a participant in the UK reportedly developing symptoms related to a transverse myelitis, a rare spinal inflammatory disorder.
The US regulator is investigating the side effects. But the time delay means the time frame set out in the trial protocol submitted to the US regulator will be breached.
In a statement, AstraZeneca said: “On 6 September, the standard review process triggered a voluntary pause to vaccination across all global trials to allow review of safety data by independent committees and international regulators.
“All trial investigators and participants will be updated with the relevant information and this will be disclosed on global clinical registries, according to the clinical trial and regulatory standards.”
However, the trial in the UK resumed in early September but was halted for a second time last week. But the Medicines Health Regulatory Authority (MHRA) in the UK confirmed that it was safe to continue the trial in the UK.
Agreements with governments
To date, AstraZeneca has signed agreements to supply nearly three billion doses of the COVID-19 vaccine to governments around the world.
Work on the Oxford Vaccine Centre’s COVID-19 vaccine trial, which began on 20 January, is being carried out by scientists from the Jenner Institute and the Oxford Vaccine Group, led by Professor Sarah Gilbert. Between them, the scientists have decades of experience in vaccine research, including responding to the Ebola outbreak in 2014.
The trial in the US is funded by US Biomedical Advanced Research and Development Authority (BARDA) and the National Institute of Allergy and Infectious Diseases (NIAID), part of the US National Institutes of Health, and led by AstraZeneca. The NIAID-supported COVID-19 Prevention Network (CoVPN) will participate in the trial.
A chimpanzee adenovirus vaccine vector (ChAdOx1), developed at Oxford’s Jenner Institute, was chosen as the most suitable vaccine technology for a SARS-CoV-2 vaccine as it can generate a strong immune response from one dose. It is not a replicating virus, so it cannot cause an ongoing infection in the vaccinated individual.
This also makes it safer to give to children, the elderly and anyone with a pre-existing condition such as diabetes.
Chimpanzee adenoviral vectors are a very well-studied vaccine type, having been used safely in thousands of subjects, from one week old to 90 years of age, in vaccines targeting over 10 different diseases.
Coronaviruses have club-shaped spikes on their outer coats. Immune responses from other coronavirus studies suggest that these spikes are a good target for a vaccine. The Oxford vaccine contains the genetic sequence of this surface spike protein inside the ChAdOx1 construct. After vaccination, the surface spike protein of the coronavirus is produced, which primes the immune system to attack the coronavirus if it later infects the body.
Gilbert and her team have previously developed a vaccine for another human coronavirus disease, which is Middle East Respiratory Syndrome (MERS), and this has shown promise in early clinical trials.
In April Gilbert had said “if everything goes perfectly” the vaccine could be ready by the European autumn. She told The Times that she thought there was a high chance that the trial would work, “based on other things that we have done with this type of vaccine”.
“It’s not just a hunch, and as every week goes by, we have more data to look at,” she said.
In June, WHO Chief Scientist Soumya Swaminathan suggested the Oxford-AstraZeneca as a likely leader in the race to develop a vaccine.
Since then, the optimism has been tempered by the two interruptions of trials, the latest one and an earlier one in September, although this is nothing unusual in vaccine trials.
Before those suspensions Pascal Soriot, CEO of AstraZeneca, said: “In recent weeks, we have seen an increasing number of questions around the safety and availability of vaccines to fight this terrible COVID-19 pandemic and I want to reiterate my commitment that we are putting science and the interest of society at the heart of our work.
“We are moving quickly but without cutting corners, and regulators have clear and stringent efficacy and safety standards for the approval of any new medicine, and that includes this potential COVID-19 vaccine. We will remain true to our values as we continue our efforts to bring this vaccine broadly and equitably to billions of people around the world.”
If the trials are successful, Oxford University and AstraZeneca have agreed to produce and scale up distribution of the vaccine.
“We will be working closely with our partners and the British government to ensure the vaccine is made available as quickly and fairly as possible and in sufficient quantities to vaccinate the entire UK population,” the group says.
“As part of our agreement with AstraZeneca, we are ensuring that those countries which are most vulnerable to the worst effects of this global pandemic have early access to a vaccine.”
The WHO says nearly 180 vaccine candidates are being tested around the world.