A silly mistake increased the Oxford coronavirus vaccine’s efficacy

  • Researchers made a critical mistake early in the development of the Oxford coronavirus vaccine trial, which led to an unexpected result.
  • Some 3,000 people received half a dose of the vaccine, followed by a full dose four weeks later. This regimen yielded an efficacy of 90%, much better than the efficacy of two full doses of the drug.
  • The researchers are trying to determine what triggers the improved immune response when only half a dose is administered initially and whether the resulting immune response can be considered satisfactory.

AstraZeneca and Oxford announced Phase 3 interim data on Monday for their experimental coronavirus vaccine, revealing that the drug is 70% effective on average. Pfizer and Moderna both reported similar efficacy, which is even better than Oxford’s results. At 95%, the Pfizer and Moderna vaccines seem much better suited to protect against coronavirus infection or severe COVID-19 disease than Oxford’s drug. However, the Oxford candidate does have two important advantages over the other drugs.

The vaccine is cheaper to mass produce and will be significantly more affordable to governments. The Oxford drug can also survive at regular fridge temperatures, which means it can be transported and distributed easier than the others. In an unexpected twist, it seems that the Oxford drug can reach 90% efficacy. It’s all thanks to a mistake the researchers involved in testing made, once that can be replicated with ease in actual vaccination campaigns if the results are indeed as promising as the interim data says.

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The Oxford trial arm that reached 90% efficacy consisted of a limited cohort of about 3,000 people who received two doses of the drug, like other volunteers. What was different, however, was the concentration of those doses. The group of 3,000 got a half-dose initially, followed by a full dose a few weeks later. Everyone else in the trial received two full doses a few weeks apart.

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

When university researchers distributed the vaccine at the end of April when the Oxford-AstraZeneca partnership started, they noticed the side effects were milder than expected — this included fatigue, headaches, or arm aches.

“So we went back and checked … and we found out that they had underpredicted the dose of the vaccine by half,” Pangalos said.

Instead of restarting the trial, the researchers ahead and administered the full dose booster shot at the scheduled time, four weeks later. This regimen yielded a 90% efficacy. According to interim data, the group who received two full doses four weeks apart got a 62% efficacy.

Scientists can’t explain the striking difference but plan to study the matter further and see whether the immune response in the 3,000-person cohort is satisfactory. What seems to be clear is that the two different regimens trigger the immune response differently in volunteers.

“It could be that by giving a small amount of the vaccine to start with and following up with a big amount, that’s a better way of kicking the immune system into action and giving us the strongest immune response and the most effective immune response,” Oxford professor Sarah Gilbert told The Guardian.

“What we don’t know at this moment is whether that difference is in the quality or the quantity of immune response. And that’s something we’re going to be digging into over the next weeks,” added Oxford professor Andrew Pollard, the director of the Oxford Vaccine Group.

The vaccine has to be approved by regulators before it can be used on the public at large. AstraZeneca inked contracts for 3 billion vaccine doses. It’s unclear which immunization regimen will be used by the general public once the vaccine is approved. The limited 3,000-person cohort is only a small part of the trial. Oxford will have to show results for 30,000 volunteers to get approvals in the US.

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