Oxford COVID vaccine paper highlights lingering unknowns about results - Nature.com

Credit: Juan Mabromata/AFP/Getty

The first formally published results from a large clinical trial of a COVID-19 vaccine — which scientists hope could be among the cheapest and easiest to distribute around the world — suggest that the vaccine is safe and effective. But the data also highlight a number of lingering unknowns, including questions about the most effective dosing regimen and how well it works in older adults.

The vaccine, developed by the University of Oxford, UK, and the pharmaceutical firm AstraZeneca in Cambridge, UK, has been closely watched, in part because it is likely to be simpler to distribute than the two RNA-based vaccines from companies Pfizer and Moderna, which need to be stored at low temperatures. The Oxford team is also now the first among these three leading vaccine developers to publish its results in a peer-reviewed journal — so far, findings from phase III trials have been disseminated only through press releases.

The UK has approved a COVID vaccine — here’s what scientists now want to know

Researchers have been eager to delve into the details of Oxford’s results, which were published in The Lancet¹ on 8 December, after preliminary results released last month showed an unexpected increase in efficacy among a subset of study participants who, due to a measurement error, received a lower initial dose of two-dose vaccine regimen. Some statisticians also raised concerns that the study pools data from different trials, rather than drawing from a single study.

Dosing puzzle

When the various dosing regimens were combined, the study found that the vaccine was 70% effective against symptomatic coronavirus infections. The standard dosing regimen — two doses of the same strength administered a month apart — had an efficacy of 62%, whereas the regimen with a lower initial dose yielded an efficacy of 90%. “The efficacy and the safety are fine,” says virologist Stephen Griffin of the University of Leeds, UK. “Overall, what you can say is that it does work.”

At a press briefing on 8 December, study investigators said that the data was pooled in agreement with guidance from regulators. However, researchers have struggled to explain how a higher efficacy could be achieved from a lower initial dose, and trial investigators have said a separate trial is needed to follow up on the finding. The low-dose arm of the trial also did not include anyone over the age of 55, raising concerns that the higher efficacy was merely a by-product of excluding an age group that is particularly vulnerable to COVID-19.

But reviewers of the Lancet paper asked the team to break down their data by age, which revealed that the efficacy in adults under the age of 55 was still higher in the low-dose group than among those who received the standard dose, says Andrew Pollard, director of the Oxford Vaccine Group at the University of Oxford.

Overall, it remains unclear how much the over-55 age group will benefit from even the standard dose of the vaccine: only 12% of those evaluated for vaccine efficacy were over 55. Earlier studies of the vaccine showed that immune responses in people over 55 were comparable to those of younger study participants, suggesting that the vaccine will work well in older adults. But the larger clinical trial has little data from older adults so far because they were recruited to the study later, says Pollard. The results published today are interim data from more than 11,000 of the roughly 24,000 participants enrolled, and researchers might learn more about the vaccine in older adults as data from the remaining participants come in.

Symptomless infections

Another lingering question is whether the vaccine is capable of fighting asymptomatic infections; an immunization that could prevent these could be key to shaping the course of the pandemic. The Oxford–AstraZeneca team is the only one of the three leading vaccine developers that monitored for asymptomatic infections in participants, by collecting weekly swabs to determine whether they had the coronavirus but did not become ill. The data show that the low-dose vaccine regimen was about 60% effective in reducing asymptomatic infections, but it was unclear whether the standard dose significantly reduced such infections at all.

Researchers are concerned about asymptomatic infections because people who have such infections might unknowingly continue to transmit the virus others in the community, despite being vaccinated. Although asymptomatic infections are not a direct measure of disease transmission, researchers have looked to this data as an indication of how much vaccines might affect the spread of COVID-19. “For now, this is the only study that’s given us data on that,” says Griffin. “And it’s a bit troubling.”

The two leading RNA vaccines have not gathered data on asymptomatic infections, but they have been more than 90% effective in preventing symptoms of COVID-19. And even if the efficacy of the Oxford vaccine proves to be lower than those of the other two, it is still likely to be beneficial, says Griffin. The lower efficacy has to be balanced against the practicalities of vaccinating everyone who needs it, he adds. “It’s going to come down to a cost-benefit analysis,” he says.

Oxford and AstraZeneca have agreed to provide the vaccine to buyers for US$2–$3 per dose. And the vaccine is comprised of DNA encoding a coronavirus protein that is shuttled into cells in a harmless virus, a product that will be cheaper and easier to make in bulk than the RNA vaccines from Pfizer and Moderna, says Griffin. It also does not need to be stored at temperatures as low as the RNA vaccines, one of which must be kept at –70 ºC much of the time until it is administered.

More than one

And the scale of the pandemic means that it will be crucial to have more than one COVID-19 vaccine, said AstraZeneca chief executive Pascal Soriot at a press briefing. Combined, the planned number of doses from Moderna, Pfizer and AstraZeneca would still not be enough to vaccinate the world. “It is really important to have several vaccines,” he said.

Oxford’s data comes on the same day that the United Kingdom began administering the Pfizer and BioNTech vaccine outside of trials, less than a week after UK regulators became the first to grant an emergency-use authorization to one of the major vaccines.

The Oxford data have now been submitted to regulators around the world, said Mene Pangalos, AstraZeneca’s executive vice-president of biopharmaceuticals research and development at a press briefing.

In the United States, a panel of advisers to the Food and Drug Administration (FDA) will meet on 10 December to discuss the Pfizer–BioNTech vaccine, and an emergency-use authorization is expected to follow shortly afterward. Moderna, which is based in Cambridge, Massachusetts, also announced positive clinical-trial results last month for its vaccine, which FDA advisers will discuss on 17 December.

Let's block ads! (Why?)

"about" - Google News
December 09, 2020 at 02:04AM
https://ift.tt/2Ire2ef

Oxford COVID vaccine paper highlights lingering unknowns about results - Nature.com
"about" - Google News
https://ift.tt/2MjBJUT


Bagikan Berita Ini