Study: 3-Month Interval Between Oxford COVID-19 Vaccine Doses Results in Higher Efficacy

New exploratory analyses have found that a longer interval between the first and second standard dose of Oxford University’s COVID-19 vaccine candidate results in higher efficacy compared to a shorter 6-week interval.

Investigators also found that the first dose offers significant protection in the 3 months between doses, with 76% efficacy. The results, published in The Lancet, suggest that the interval between doses can be safely extended given the protection offered by the first dose, which may allow countries to vaccinate a larger proportion of the population more rapidly, according to the study.

The exploratory analyses included 17,178 participants as well as updated estimates of overall vaccine efficacy against symptomatic disease for 2 standard doses. According to a press release, there were no hospitalizations or deaths among those receiving the vaccine from 22 days after the first dose, compared with 15 cases in the control group. The study authors said this provides further support for the vaccine candidate and its extended intervals between doses.

“Vaccine supply is likely to be limited, at least in the short term, and so policy-makers must decide how best to deliver doses to achieve the greatest public health benefit,” said lead author Andrew Pollard, BSc, MBBS, PhD, in the press release. “Where there is a limited supply, policies of initially vaccinating more people with a single dose may provide greater immediate population protection than vaccinating half the number of people with 2 doses.”

Following regulatory approval, the investigators said it is important to understand the best dose interval in order to ensure optimal roll-out plans. Factors associated with this include the effect of different intervals on protection after the second dose, and the risk of infection between doses either due to lower efficacy of a single dose or rapid waning of efficacy while waiting for the second dose, according to the study.

The investigators combined data from randomized controlled trials in the United Kingdom, Brazil, and South Africa. Participants were aged 18 years or older and either received 2 doses of the Oxford COVID-19 vaccine candidate or a control vaccine and saline combination. In the United Kingdom trial, a subset of participants received a lower dose of the vaccine as their first dose.

The primary outcome was the number of symptomatic COVID-19 cases in the control and vaccine groups occurring more than 14 days after the second dose. The exploratory analyses were requested by regulators and policymakers. The investigators also conducted an analysis to establish the impact of 1 or 2 doses of the vaccine on reducing all COVID-19 cases as an indicator of how the vaccine might reduce transmission.

According to the press release, participants who were given their doses 12 or more weeks apart had 81% protection, compared to 55% efficacy for those given their 2 doses less than 6 weeks apart. Efficacy results were supported by immune response results in adults between 18 and 55 years of age, which showed that binding antibody responses were more than 2-fold higher in the group having their 2 vaccines with a longer delay.

Following a single standard vaccine dose, efficacy from 22 days to 3 months after vaccination was 76%. Modeling indicated that this protection did not reduce over the 3 months, and antibody levels against the SARS-CoV-2 spike protein remained at similar levels throughout the interval period.

“This latest analysis confirms our previous findings of the higher efficacy of a low- then standard-dose regimen,” said Merryn Voysey, PhD, lead statistician at the Oxford Vaccine Group, in the press release. “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.”

The investigators noted that it is unclear how long protection with a single dose of the vaccine might last because the trial results are limited to the 3 months maximum. For this reason, the investigators said a second dose of the vaccine is still recommended.

“This further supports the relationship we have found between vaccine interval and efficacy in those receiving 2 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,” Voysey said.

REFERENCE

The Lancet: 3-month interval between first and second dose of Oxford COVID-19 vaccine results in higher vaccine efficacy than 6-week interval [news release]. EurekAlert; February 19, 2021. https://www.eurekalert.org/pub_releases/2021-02/tl-pss021921.php. Accessed February 23, 2021.