Oxford vaccinologists were thrilled on Monday when drugmaker AstraZeneca, with whom they developed the injection, announced that it could be around 90% effective, citing data from late-stage trials.
“It can only happen if you provide extraordinary support,” Adrian Hill, director of the Jenner Institute at the University of Oxford, who developed the shot, told Reuters. “We got the whole Oxford institute working on this vaccine pretty well.”
While skill and hard work drove development, AstraZeneca said it was a minor mistake that made the team realize how they could significantly increase the injection success rate, up to 90% from around 60%: administering half a dose, followed by a full dose one month later.
“The reason we take half the dose is chance,” Mene Pangalos, AstraZeneca’s head of non-cancer research and development, told Reuters.
The plan was for trial participants in Britain to receive two full doses, but the researchers were stumped when they noted that side effects, such as fatigue, headaches or arm aches, were milder than expected, Pangalos said.
“So we went back and checked … and found they had underestimated the vaccine dose in half.”
Nonetheless, he said, the team decided to go ahead with that half-dose group and give the second full-dose booster injection at the scheduled time.
The results showed that the vaccine was 90% effective among this group, while a larger group that had received two full doses produced an efficacy reading of 62%, leading to an overall efficacy of 70% in both dosing patterns. said Pangalos.
“This is, in essence, how we came across doing (group) half dose-full dose,” he told Reuters. “Yes, it was a mistake.”
The vaccine uses a harmless adenovirus to deliver genetic material that tricks the human body into producing proteins known as antigens that are normally found on the surface of the coronavirus, helping the immune system develop an arsenal against infection.
Pangalos said more analysis was needed to explain why a lower starting dose enhanced protection. One possible explanation was that lower antigen levels triggered better overall immune system development to begin with, he added.
1991 to today
Although good luck played its part, the development of what Oxford scientists hailed as “a vaccine for the world” was based on 30 years of testing and method adjustments.
The adenovirus “viral vector” platform your candidate uses has been around since 1991, said Hill of the university’s Jenner Institute.
He had been working with Sarah Gilbert, another vaccinologist, to fine-tune the technology. This has involved the use of a chimpanzee cold virus as a vector to transmit instructions, in trials with diseases such as influenza, MERS and Ebola over the last decade. The hope was that one day it would prove its potential against one or more of these deadly diseases.
They turned their attention to the new coronavirus, SARS-CoV-2, in January. Oxford Vice Chancellor Louise Richardson said she was told about Gilbert’s work and that it looked promising for the new coronavirus, but that he was operating on very little money.
The university then offered a million pounds to fund the research until more funds were added, Richardson told reporters, which duly came when the government and AstraZeneca got involved in May.
The unprecedented urgency and resources given to Oxford to demonstrate the platform’s effectiveness against COVID-19 meant that it outperformed vaccines against those other pathogens, which are still in trials in their early stages.
Gilbert said the experience with MERS, or Middle East respiratory syndrome, which is caused by a different type of coronavirus, was especially instructive.
“It showed us that we could make a vaccine with this technology that would induce good immune responses against the coronavirus spike protein,” he told reporters.
“We had also been thinking about how to act very quickly when a new pathogen emerges and we need to make a new vaccine. We did a job preparing for that.”
2020: ‘A very long year’
Andrew Pollard, director of the Oxford Vaccine Group and a professor who has spent two decades conducting clinical trials, said this experience gave him confidence in the prospects for Oxford’s new vaccine, initially known as ChAdOx1 nCoV-19.
“I think we knew since the beginning of the year that if we could go through this development, we might as well have something that could make a difference,” Pollard told Reuters.
But there was a problem. Limited interest in Oxford’s vaccines for other pathogens before this year meant they didn’t have the funds to demonstrate the platform’s effectiveness – until now.
“It takes a lot of money or a pandemic to bring in that resource, and it is tremendous that we have had this opportunity to validate the chimpanzee adenovirus technology for this coronavirus,” Hill said.
“If they had told me a year ago that in 2020 anyone would make a vaccine for a global pandemic, and in months instead of years, I would have thought it was a big challenge.”
Pollard said that while the speed of development of the COVID-19 vaccine was somewhat extraordinary, 2020 had “been a very long year” since the team began work on the vaccine in January.
That culminated last weekend, Pollard said, having “a huge mountain to climb to gather all the information” to be able to issue Monday’s data release showing the vaccine can be up to 90% effective.
“The past few weeks have been quite exhausting. The feeling is absolutely one of extreme fatigue and exhaustion at this point,” he told Reuters, speaking before briefing British Prime Minister Boris Johnson’s office on the findings.
“If the results hadn’t met the regulatory requirements, they would have told us to continue testing. So it was a huge relief.”
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