45-week gap between Oxford coronavirus vaccines triggers 'enhanced immune response'

Vaccination of senior person in hospital
Administering the two Oxford-AstraZeneca coronavirus vaccine doses 45 weeks apart could boost an individual's immune response. (Stock, Getty Images)

Waiting almost a year between the first and second University of Oxford-AstraZeneca coronavirus vaccines leads to stronger protection against the infection, research suggests.

The jab was approved after a study demonstrated it is up to 90% effective at warding off COVID-19, the disease caused by the coronavirus, when administered with a three-week interval between the doses.

In the UK, the interval was extended to up to 12 weeks to maximise the number of people receiving their first dose. Many experts were optimistic this would better "prime" the immune system, leading to greater protection overall.

Scientists from the University of Oxford have now revealed a 45-week gap between the vaccines may trigger a more "enhanced immune response" still.

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Administering a third "booster" jab six months after the second vaccine also causes a "substantial increase" in an individual's immune cells, the results – which have not yet been published in a peer-reviewed journal – suggest.

Illustration of antibodies (y-shaped) responding to an infection with the new coronavirus SARS-CoV-2. The virus emerged in Wuhan, China, in December 2019, and causes a mild respiratory illness (covid-19) that can develop into pneumonia and be fatal in some cases. The coronaviruses take their name from their crown (corona) of surface proteins, which are used to attach and penetrate their host cells. Once inside the cells, the particles use the cells' machinery to make more copies of the virus. Antibodies bind to specific antigens, for instance viral proteins, marking them for destruction by other immune cells, such as the macrophage white blood cell behind the virus.
A longer interval between the two jabs may increase antibodies, infection-fighting proteins that circulate in the blood. (Stock, Getty Images)

"This should come as reassuring news to countries with lower supplies of the vaccine, who may be concerned about delays in providing second doses to their populations," said lead investigator Professor Sir Andrew Pollard.

"There is an excellent response to a second dose, even after a 10-month delay from the first."

The World Health Organization recommends a second coronavirus jab be given eight to 12 weeks after the first vaccine, "since the clinical trial data provide support for good levels of protection with this dose interval".

Vaccine shortages in less-developed countries has caused concern an individual's immunity may be "compromised" if the second jab is given beyond 12 weeks.

Read more: Vaccines 'still offer substantial protection' against Delta variant

The UK has four coronavirus jabs in its immunisation arsenal against the pandemic – Oxford-AstraZeneca, Pfizer-BioNTech, Moderna and the recently approved single-dose Janssen.

The scientists only analysed the Oxford-AstraZeneca jab, of which more than half a billion doses have been distributed to over 160 countries across six continents.

This Oxford-AstraZeneca vaccine has less stringent storage requirements than the Pfizer-BioNTech and Moderna jabs and can therefore be more easily distributed worldwide.

The Oxford scientists had 30 volunteers – aged 18 to 55 – receive a "late second dose" of the Oxford-AstraZeneca vaccine, around 45 weeks after their first jab.

The results reveal extending the vaccine interval boosted the volunteers' antibodies, infection-fighting proteins that circulate in the blood, compared with those who waited just eight to 12 weeks for their second jab.

Antibodies can wane over time, with studies throwing up mixed results when it comes to how a patient's immune response may deteriorate post-vaccine.

Read more: Oxford's coronavirus jab linked to bleeding disorder in rare cases

The emergence of new coronavirus variants has prompted some to wonder whether a booster jab will be required, developed according to the variant that is dominant at that time.

To learn more, the scientists gave the same Oxford-AstraZeneca vaccine – based on the original coronavirus variant that emerged in Wuhan, China, at the end of 2019 – as a third dose to 90 volunteers.

The volunteers' antibody response was "significantly" higher after a third jab, compared to 28 days after the second vaccine.

A third vaccine was also found to boost other aspects of the immune system, like so-called T cells.

In addition, the booster produced antibodies against the Alpha, Beta and Delta variants, which emerged in the UK, South Africa and India, respectively.

"It is not known if booster jabs will be needed due to waning immunity or to augment immunity against variants of concern," said co-lead author Dr Teresa Lambe.

"Here we show a third dose of [the Oxford vaccine] is well tolerated and significantly boosts the antibody response."

Side effects were found to become less common after the second and third doses.

The Oxford-AstraZeneca jab has long been linked to an unusual form of blood clot, defined by low numbers of blood clotting cells called platelets. "Recent information from Public Health England indicates this very rare event does not occur after a second dose", wrote the scientists.

Speaking of the study, Dr Lambe concluded: "This is very encouraging news, if we find a third dose is needed."

The scientists have stressed the third-dose recipients need to be followed for longer to determine if their immune response lasts.

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