No half steps and mind the gap: More concerns are posed by UK nod for AstraZeneca vaccine

LONDON (Reuters) -British health officials greenlighted the Wednesday shots of AstraZeneca and Oxford COVID-19 but also dismissed one of their key claims: that a half-dose accompanied by a regular dose provided more infection protection.

The reassessment of the best vaccine dosing scheme was an unusual development based on its own review of as-yet-unpublished data by the British Medicines Regulator and raised new concerns about the safety of a vaccine that has yet to be licensed in other countries.

While cheaper and easier to administer than competing shots, because data published last month showed a half-dose followed by a full dose had a 90 percent success rate, whereas two full shots were 62 percent successful, the Oxford/AstraZeneca vaccine has been plagued with confusion over the most effective dosage.

Oxford researchers said that a "intriguing result" that merited further study was the more promising outcome.

However, a Reuters investigation found that the presence of the low-dose/standard-dose arm was the result of Oxford researchers' miscalculation of potency, casting doubt on the robustness of the outcome.

On Wednesday, Munir Pirmohamed, chair of the British COVID-19 vaccine advisory committee, validated those suspicions, stating that the 90 percent efficacy figure did not hold up under review.

Instead, Pirmohamed said that a higher success rate could be due to a longer delay between the first and second shots being administered.

While it has been cited that the low dose/standard dose protocol has an efficacy of 90%, this is confounded by the fact that the period between the first and second dose was very long," Pirmohamed told a news conference."

"And we feel that that outcome, rather than the dose itself, may be related to that interval," he said.

Wei Shen Lim, chair of the UK COVID-19 vaccine, said a single dose of the Oxford/AstraZeneca vaccine was approximately 70 percent effective from 21 days before a second dose was given.

Pirmohamed said that leaving the three-month difference between doses rather than a one-month gap might increase the AstraZeneca/Oxford vaccine's success rate to 80% .

After the new information about the effectiveness of the vaccine were released by British health authorities, an AstraZeneca spokesman said: "It is for the regulators to authorize how the vaccine should be used."

"Comparable immunogenic response after two doses with either regimen, as well as protection against severe disease (100%), are factors to be taken into account," he said.

"We believe we have the best MHRA approved vaccination strategy."

In the face of a record increase in infections triggered by a highly infectious strain of the virus, Britain prioritizes giving as many individuals as possible a first dose of a vaccine over giving second doses. Stretching the supply would help delay the delivery of second shots.

An interval of 4-12 weeks between doses of the AstraZeneca/Oxford vaccine was recommended by the British Medicines and Healthcare Products Regulatory Agency (MHRA) and its guidance for a second dose of the Pfizer-BioNTech shot was also updated, stating that it could be administered within 12 weeks, rather than the originally recommended 21 days.

The first dose of Pfizer vaccine has already been obtained by hundreds of thousands of Britons since the UK was the first country to authorize its roll-out, with second doses expected from this week.

Pfizer seemed wary about the possibility of adjusting the timing of its second dose, adding that various dosing schedules had not been assessed.

'There is no evidence to show that safety after the first dose is preserved after 21 days,' it said in a statement, adding that it is important to track closely the implementation of alternative schedules.

"While health authorities are responsible for decisions on alternative dosing regimens, Pfizer believes it is important... To ensure that the best possible protection is afforded to each recipient, which requires immunisation with two doses of vaccine.

"In Britain's Sunday Times newspaper, AstraZeneca CEO Pascal Soriot was quoted as saying that his company had a "competitive recipe" to rival the efficacy rates of about 95 percent shown by Pfizer and Moderna vaccines. He confirmed that he could not say more pending the release of new data.

Oxford vaccine creator Sarah Gilbert, speaking to Sky News, said there was accountability in the process.

"The MHRA has said that their evaluation report will be released. Within the experiment, there are different classes, we have had different dose periods and different dose levels, as you said, and that makes the study a little difficult,' she said.

"The MHRA has done its own analysis, and they are very confident that the vaccine will be licensed for emergency use now."

Following the MHRA briefing, Oxford did not respond to a request for comment.

Regulators have taken a more cautious approach in other countries than Britain, and the numerous efficacy rates cited by the MHRA, as well as its recent guidelines on the timing of second doses, have prompted scientists to call for the release of the specifics underpinning its approval.

More needs to be understood, as several things remain vague regarding these decisions. Saad Shakir, Director of the Drug Safety Research Unit near Southampton, said that MHRA and JCVI vowed to provide more information urgently.

Jeremy Farrar, Director of Wellcome Health Research Foundation, said there may be a need for a new trial to provide clearer data on the best timing of a second dose.

"We will also need to continue to monitor and enhance our understanding of how long the protection lasts and whether transmission can be prevented," he said.

"A randomised trial on the timing of the second dose would best achieve this."