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New research suggests that a 12-week gap between doses of the Oxford-AstraZeneca vaccine might be better than a shorter interval.
  • The efficacy of some COVID-19 vaccines relies on having two doses within a certain amount of time.
  • The government of the United Kingdom decided to leave a 12-week interval between doses of the Oxford-AstraZeneca vaccine.
  • A new analysis of trial data suggests that a 12-week gap “might” be more effective than shorter intervals.

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Researchers have reanalyzed the Oxford-AstraZeneca vaccine trial findings, this time with an additional month of data. They confirm that the vaccine is safe and effective, just as the interim analysis had suggested.

However, using this data, they have also been able to explore the relative efficacy of different intervals between doses of the vaccine.

The analysis has also revealed information about the effectiveness of a single dose of the vaccine over a 12-week period.

The research, published in The Lancet, will help inform health policy as governments weigh the urgency of offering both doses against the relative scarcity of vaccine supplies.

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Certain vaccines developed in response to the COVID-19 pandemic are safe and effective, researchers have shown.

In some cases, as with the Pfizer-BioNTech, Moderna-NIAID, and Oxford-AstraZeneca vaccines, top effectiveness is achieved when a person receives two doses a number of weeks apart.

However, there is some concern that vaccines are in short supply and that vaccination centers may be unable to meet the demand. This could force governments to choose between vaccinating fewer people in a short period or more people over a longer time.

The U.K. government has decided to maintain a relatively long gap of up to 12 weeks between doses of the Oxford-AstraZeneca vaccine. The hope is that giving more people the initial dose right away will lead to fewer deaths and less pressure on the country’s already overwhelmed emergency services.

In the present study, the researchers wanted to confirm the interim results of the Oxford-AstraZeneca vaccine trial, with an additional month’s worth of data.

In addition, regulatory agencies and policymakers asked the team to investigate the efficacy of a single dose and the relative efficacy of 6- and 12-week booster dose intervals.

The researchers analyzed data from four randomized controlled trials, which were part of the initial Oxford-AstraZeneca vaccine trials. The team looked at data from 17,178 participants in trials from the U.K., Brazil, and South Africa.

Since the interim findings, an additional month’s worth of data has been collected. This allowed the researchers to confirm the interim results, which found the Oxford-AstraZeneca vaccine to be safe and effective.

Because of the ways that these trials were conducted, a number of factors enabled the researchers to analyze the efficacy of a single dose of the vaccine, as well as the relative efficacy of 6-week and 12-week dose intervals.

Studies of the Oxford-AstraZeneca vaccine began as investigations of a single dose. They were then expanded to include two doses.

Some people who had signed up to participate in a single-dose study did not choose to have the second dose. This provided the researchers with data to compare the effects of single and double doses.

Also, because manufacturing the second dose took time, and there were delays, the team had data from a variety of dosage intervals to analyze.

The additional month of data confirmed that the Oxford-AstraZeneca vaccine is safe and effective, the researchers found.

In their exploratory analyses, they also determined that a second dose after 12 weeks might be more helpful than a second dose after 6 weeks.

“Programs aimed at vaccinating a large proportion of the population with a single dose, with a second dose given after a 3-month period, might be an effective strategy for reducing disease and might have advantages over a program with a short prime-boost interval for roll-out of a pandemic vaccine when supplies are scarce in the short term,” the researchers write.

The 12-week interval was 81% effective, compared with 55% for the 6-week interval. The researchers also found that a single dose of the vaccine was 76% effective 3–12 weeks after the shot was administered.

And, in line with the interim trial results, the researchers observed that a low dose of the vaccine followed by a normal dose was more effective than two normal doses.

According to Dr. Merryn Voysey, the lead statistician at the Oxford Vaccine Group and a lead author of the study, “This latest analysis confirms our previous findings of the higher efficacy of a low- then standard-dose regimen.”

“However, with additional data available, we have found that the enhanced efficacy and immunity may be partly driven by the longer interval between doses that was common in this trial group,” she adds.

Dr. Voysey continues: “This further supports the relationship we have found between vaccine interval and efficacy in those receiving two standard doses, which is the preferred regimen because there are more data to support its use and because it is simpler to deliver a vaccine program when the same vaccine is given for both doses.”

The researchers also found evidence that the vaccine may reduce transmission — as a single dose or two doses.

As Prof. Andrew Pollard, director of the Oxford Vaccine Group and another lead author of the study, notes, “It is important to understand whether vaccines can reduce COVID-19 transmission.”

“While specific transmission studies were not included in our analysis, U.K. trial participants were tested for COVID-19 each week, regardless of symptoms, and we combined this with other positive COVID-19 cases in the trial to help determine the overall impact of the vaccine on risk of infection,” he notes.

“If the vaccine had no impact on transmission, we would expect that the number of positive tests in our trial would be the same in vaccine and control groups. This is because the vaccine would convert severe cases to mild cases, and mild cases to asymptomatic cases.”
– Prof. Andrew Pollard

“However, we saw a reduction in the overall number of positive cases, which indicates that the vaccines may reduce infections. Real-world assessments of how the vaccine is working in the population will be needed to confirm this preliminary result,” Prof. Pollard acknowledges.

The researchers stress that these are exploratory results and that — because the initial trials were not designed to investigate these findings — there are limits to how definitive their conclusions can be.

Nonetheless, they believe that their findings provide valuable information for policymakers attempting to weigh limited vaccine supplies against the need to protect as many people as possible from COVID-19.

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