A dosing error during late-stage trials allowed Oxford coronavirus scientists to realise they had created a 90 percent-effective vaccine.
Drugmaker AstraZeneca – which partnered with the University of Oxford to manufacture the vaccine – announced the results on Monday following months of research and testing.
And while it took the university’s brightest minds decades of work to give them the expertise, in the end it was a momentary error that carried them over the line.
The mistake meant the team of vaccinologists realised they could significantly boost the shot’s success rate by as much as 30 percent by administering a half dose, followed by a full dose a month later.
“The reason we had the half dose is serendipity,” Mene Pangalos, head of AstraZeneca’s non-oncology research and development, said.
The plan was for trial participants in Britain to receive two full doses, but researchers were perplexed when they noticed that side effects, such as fatigue, headaches or arm aches were milder than expected, Pangalos said.
“So we went back and checked…and we found out that they had under-predicted the dose of the vaccine by half.”
He said the team nonetheless decided to press ahead with that half dose group, and to administer the second, full dose booster shot at the scheduled time.
The results showed the vaccine was 90 percent effective among this group, while a larger group who had received two full doses produced an efficacy read-out of 62 percent, leading to an overall efficacy of 70 percent across both dosing patterns, Pangalos said.
“That, in essence, is how we stumbled upon doing half dose-full dose [group],” he said. “Yes, it was a mistake.”
The vaccine uses a harmless adenovirus to deliver genetic material that tricks the human body to produce proteins known as antigens that are normally found on the coronavirus surface, helping the immune system develop an arsenal against infection.
Pangalos said more analysis was needed to explain why an initial lower dose bolstered protection.
One possible explanation was that initially lower antigen levels triggered an overall better immune system build-up, he added.
Even though good fortune played its part, the development of what Oxford scientists hailed as “a vaccine for the world” was built upon 30 years of testing and tweaking of methods.
The adenovirus “viral vector” platform that their 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 using a chimpanzee cold virus as the vector to deliver the instructions, in trials with diseases such as flu, MERS and Ebola over the last decade.
The hope was that it would one day prove its potential against one or more such deadly diseases, and they turned their attention to the new coronavirus, SARS-CoV-2, in January.
Pollard said that while the speed of the Covid-19 vaccine’s development was in some ways extraordinary, 2020 had “been a very long year”.
Months of work culminated this past weekend, Pollard said, in having “an enormous mountain to climb to pull all of the information together” to be able to issue Monday’s data release showing the vaccine can be up to 90 percent effective.
“The last few weeks have been pretty exhausting. The feeling is absolutely one of extreme fatigue and tiredness at this point,” he said, speaking before he briefed the office
of Prime Minister Boris Johnson on the findings.
“If the results had not met those regulatory requirements, they would have told us just to carry on with the trial. So it was a great relief,” he added.