In Depth

Coronavirus: inside the ‘ten-month marathon’ to produce Oxford vaccine

Team behind university’s Covid jab admit the 90% effective dosage was discovered by mistake

While most of the world descended into panic when the coronavirus pandemic first emerged, a group of scientists at Oxford University were springing into action to develop a vaccine to fight Covid-19.

Although late-stage trials indicate that competing vaccines from Pfizer and Moderna are slightly more effective, the Oxford jab has been heralded as a potential game-changer thanks to its ease of storage and lower price tag. 

As countries including the UK now line up to reserve millions of doses, the director of the Oxford Vaccine Group, Andrew Pollard, said: “We have a vaccine for the world... this is an incredibly exciting moment for human health.” 

Lesson in team work

The Oxford vaccine’s origin can be traced back to a meeting of the university’s academics in early February. “In China, a new virus was spreading rapidly. Soon it would be here,” says The Times. “This was it: the ‘disease X situation’.”

Following the meeting, Sarah Gilbert,  a professor of vaccinology at the university’s Jenner Institute, was put in charge of the scientists tasked with creating a vaccine to combat the then unknown virus.

The formation of the research team would set in motion what the newspaper describes as a “ten-month coronavirus marathon”.

“We had recently started thinking about an appropriate response to Disease X - how could we mobilise and focus our resources to go more quickly than we had ever gone before,” Gilbert recalls. “And then Disease X arrived.” 

Also in that initial meeting with her were “Adrian Hill, a colleague in the Jenner vaccine institute, and Andrew Pollard, who had no academic expertise in the vaccine platform”, The Times reports. “His expertise, instead, was in something in its own way just as fiendishly complex: running large-scale clinical trials.”

How the jab was developed

In March, as the severity of the outbreak became increasingly apparent, Gilbert’s team was awarded a £2.2m grant from the UK’s National Institute for Health Research and the UK Research and Innovation funding agency. 

This financial backing allowed Gilbert “to scale up her team’s efforts to move into coronavirus disease 2019 vaccine preclinical and clinical trials”, as The Lancet reported the following month. 

Her team were also granted ethical approval for a clinical trial and conditional approval from the UK Medicines and Healthcare products Regulatory Agency to screen volunteers for trial enrolment.

“Ideally, we need the clinical trial to be taking place when the majority of volunteers have not been exposed to the virus,” Gilbert told The Lancet. “We will exclude volunteers who have a positive PCR test for Sars-CoV-2, or who have had fever or cough in the past month.” 

After animal trials had shown that the vaccine was safe, the researchers began human trials on 23 April. A week later, the team partnered with Cambridge-based pharmaceutical giant AstraZeneca to enable mass production and rollout of the vaccine if the trials proved successful.

Trials and tribulations

The testing process for the Oxford jab was split into the usual three phases designated for clinical vaccine trials

In Phase 1, the vaccine is tested on a small number of people to check whether it is safe. This is followed by a Phase 2 trial in which more more people are tested, and then Phase 3, which the BBC describes as “the big trial, involving thousands of people, to prove it actually protects people”.

The Oxford vaccine has now completed all three stages, with a total of 30,000 volunteers in the UK, US, Brazil and South Africa tested in Phase 3.

These final-stage trials found that the vaccine had an overall efficacy of 70.4%. But this rose to 90% among trial participants given a half dose followed by a full dose a month later, as opposed to the standard two full doses. 

The more effective dosage level was discovered by chance, after the initial half doses was administered as a result of an error.

“The reason we had the half dose is serendipity,” Mene Pangalos, executive vice-president of biopharmaceuticals research and development at AstraZeneca, told The Guardian.

After noticing that side-effects were reduced in some trial candidates, “we went back and checked… and we found out that they had underpredicted the dose of the vaccine by half,” Pangalos said. Rather than restarting the trial, the researchers decided to push ahead and administer the full dose booster as scheduled.

It is not currently known why administering a half dose first makes the vaccine more effective. 

Science journal Nature notes that the Oxford version is designed to trigger “an immune response not only to the Sars-CoV-2 spike protein, but also to components of the viral vector”. Some experts have suggested that if the first dose is administered in full, it “blunts” this reaction, making the vaccine less effective overall.

PR battle

The UK government has pre-ordered 100 million doses of the Oxford vaccine, and AstraZeneca has pledged to make a total of three billion doses for global distribution next year. 

But “now that it looks like we will have a vaccine sooner rather than later, it’s becoming clear that the PR and comms surrounding it could be just as important as the logistics of distribution”, says Wired

The next key step is to reassure “ordinary members of the public that the vaccine is safe”, and to reach out “to those who are reluctant to take it, either because of health concerns, or because they’ve been drawn into the vortex of fake news”, the magazine continues.

The importance of this PR push has been emphasised by Heidi Larson, director of the Vaccine Confidence Project.

“We need to bring the public along on the journey,” she says. “We’re at a very low trust level with our populations more broadly, and they don’t just want to know how good the product is, they want to know about the process.

“Now is the time to talk about the process, and deciding who gets it first and why.”

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