Coronavirus | Updated efficacy results show benefits of delaying second dose of Oxford vaccine

Three-month interval between doses may be effective, say researchers

Updated - December 02, 2021 10:51 pm IST

Published - February 03, 2021 02:09 pm IST - CHENNAI

 Boxes of the Oxford/AstraZeneca COVID-19 vaccine are pictured in a refrigerator at a NHS mass coronavirus vaccination centre at Robertson House in Stevenage, Hertfordshire, Britain January 11, 2021.

Boxes of the Oxford/AstraZeneca COVID-19 vaccine are pictured in a refrigerator at a NHS mass coronavirus vaccination centre at Robertson House in Stevenage, Hertfordshire, Britain January 11, 2021.


On December 30, 2020, the U.K. granted emergency use approval to the Oxford vaccine based on interim efficacy results from 131 COVID-19 cases. The U.K. regulator approved the second dose of the vaccine to be given 12 weeks after the first. Now, a preprint with updated efficacy results after a further month of data collection that includes 332 COVID-19 cases shows that delaying the second dose beyond four weeks increases the level of protection.

The data in the preprint show that vaccine efficacy was high when the interval between the two doses was two months and continued to increase with a longer dose interval. Vaccine efficacy after two standard doses increased from 54.9% when the second dose was administered less than six weeks after the first dose to 82.4% when the gap between the two doses was more than 12 weeks.

India began the mass vaccination of healthcare workers on January 16 and the expert committee set up by the Drugs Controller General of India (DCGI) has recommended that the second dose should be administered between four and six weeks after the first dose.

Better protection

According to the latest study, the longer interval between the first and second dose provides better protection without any compromise in the three-month period until the second dose is administered. They found that the vaccine efficacy against symptomatic COVID-19 after a single standard dose of the vaccine was 76% from day 22 to day 90. The antibody levels were maintained during this period with no evidence of significant waning of protection.


However, the first dose did not provide protection against asymptomatic infection in the same period. But the overall cases of PCR positive reduced by 67% after the first dose, suggesting the potential for a substantial reduction in transmission.

Participants aged 18-55 years who received the second vaccine more than 12 weeks after the first had antibody titres that were two-fold higher than those participants who received the second dose within six weeks of the first dose. The researchers also found that neutralising antibody titres measured by pseudovirus were higher after a longer interval before the second dose.

Based on the results, the researchers conclude that “vaccination programmes aimed at vaccinating a large proportion of the population with a single dose, with a second dose given after a three-month period may be an effective strategy for reducing disease, and may be the optimal for rollout of a pandemic vaccine when supplies are limited in the short term”.

Study explained


The researchers have, for the first time, explained the circumstances that led to studying the efficacy of a single dose and benefits of delaying the time before the second dose is administered. Trials involving the Oxford vaccine were initially planned as single dose studies but were later changed to include a second dose when substantial increase in neutralising antibodies were seen when a second dose was administered during the phase-1 trial. Some of the participants who initially consented to a single dose study did not choose to receive the second dose, providing a self-selected cohort of single-dose recipients.

They also report that due to the time required to manufacture the second dose, there were “delays in administration of the second dose for a large number of trial participants who received the two-dose schedule”.

“These two situations provide an opportunity to explore the immunogenicity and efficacy of a single dose of vaccine, and the impact of an extended interval before delivery of the second dose. In addition, data from an additional month of follow-up is now available for inclusion in the analysis, providing greater precision in estimates due to the larger number of cases for analysis in comparison with the previous report,” they write.

In the updated analysis, no additional hospitalisations or severe cases from 10 days after the first dose were seen in the group that received the vaccine, compared with a total of 22 in the control group.

The data cut-off date for cases to be included in the current analysis was December 7, 2020. Data to measure efficacy were taken from all four trials from the U.K. (about 8,950), Brazil (about 6,750) and South Africa (about 1,475). Totally, 17,177 participants were included in the efficacy analysis — 8,597 who received the vaccine and 8,580 control participants.

“These new analyses provide important verification of the interim data that underpinned the emergency use authorisation of the vaccine in the U.K.,” they write.

Following the approval by the U.K. regulator, many other countries, India included, approved the vaccine for emergence use.

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