A healthcare worker prepares to administer the Oxford/AstraZeneca COVID-19 vaccine to a member of the public at a vaccination centre in north LondonShare on Pinterest
A healthcare worker prepares to administer the Oxford/AstraZeneca COVID-19 vaccine to a member of the public at a vaccination center in north London, United Kingdom. Dinendra Haria/SOPA Images/LightRocket via Getty Images
  • A new study provides reassurance that a longer gap between the first and second doses of the Oxford-AstraZeneca vaccine will not compromise a person’s immune response.
  • A gap of up to 45 weeks actually led to a stronger immune response compared with the recommended interval.
  • A “booster” jab more than 6 months after the second dose further strengthened immunity, including against existing variants.
  • There were lower incidences of mild vaccine side effects after the second and third doses than after the first dose.

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Low and middle income countries, such as Bangladesh, face a resurgence of COVID-19 cases, while at the same time, their supplies of vaccines remain severely limited.

In these countries, poor vaccine supplies have led to longer gaps than recommended between the first and second doses, raising concerns about inadequate immune responses.

The World Health Organization (WHO) recommends a gap of 8–12 weeks between the first and second doses of the AstraZeneca vaccine, one of the most widely distributed vaccines, globally.

But a new study from the University of Oxford in the United Kingdom has provided reassurance that a second dose of the vaccine remains highly effective even after a gap of up to 45 weeks.

In fact, the immune response of volunteers after an extended delay was superior to the response after the recommended interval.

The study, which has yet to undergo peer review, appears as a preprint.

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The research found that a long delay may be beneficial, resulting in more antibodies to SARS-CoV-2, the virus that causes COVID-19, and an enhanced cellular immune response.

“[Y]ou get a very strong antibody induction with these really long intervals, and that’s very encouraging for countries where there may be limited supply in the short term,” said Prof. Teresa Lambe, Ph.D., one of the study’s authors, at a press briefing organized by the Science Media Centre in London.

Her co-author, Prof. Sir Andrew Pollard, Ph.D., F.Med.Sci., explained that this finding is in keeping with experience from other vaccines.

“This is fairly typical; it is what you expect from vaccines. If after you give the first dose, you give more time for the immune response to mature, you tend to see slightly better responses later on,” he said.

The study found antibody levels remained elevated up to 1 year after a single dose.

However, Prof. Pollard said that there is a trade-off between the risk of infection due to steadily declining immunity after the first dose and stronger eventual immunity after a delayed second dose.

“But we don’t really know at this moment with one dose how long you can safely sit there with still good levels of protection. But certainly, it’s longer than 3 months,” he said.

The research also showed that a third dose of the original vaccine more than 6 months after the second dose induced a strong boost to immunity against SARS-CoV-2, including the most common variants.

The third dose led to higher levels of antibodies capable of neutralizing the alpha, beta, and delta variants than were seen after the second dose.

However, the researchers emphasized that the issue of whether people would need a third “booster” dose is still very much in the air.

The latest data from Public Health England suggests that two doses of the AstraZeneca vaccine provide 92% protection against hospitalization with the delta variant.

Two doses of the Pfizer-BioNTech vaccine provide 96% protection.

Since the press briefing, the U.K. government has announced that people vulnerable to severe COVID-19 may be offered a booster vaccine from September 2021.

To assess the efficacy of a delayed second dose or a third dose, researchers vaccinated volunteers aged 18–55 years who were enrolled in a clinical trial of the AstraZeneca vaccine and had already received either one or two doses.

In total, 30 participants received a late second dose at a median of 44 weeks after the first. The scientists found that their subsequent antibody levels were higher than those who received their second dose after shorter dose intervals.

In 90 participants who received a third dose, antibody levels were higher compared with the antibody response 28 days after a second dose. Their T cell immune responses also received a boost.

Volunteers experienced less “reactogenicity” (milder side effects) to the vaccine after a delayed second or a third dose compared with the first dose.

However, the authors note some shortcomings of their study. For example, there was limited data on T cell responses after a delayed second dose.

In addition, they only measured immune responses up to 28 days after a third dose. But, they plan to follow up with volunteers at 6 months.

Finally, the current research only included younger adults, but a study of older adults is already underway.

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