Oxford first to publish peer-reviewed COVID-19 vaccine results

Interim results of the University of Oxford’s COVID-19 vaccine Phase 3 trials find that the vaccine protects against symptomatic disease in 70% of cases on average — with vaccine efficacy of 62% for those given two full doses, and of 90% in those given a half then a full dose. The results, which can be found in The Lancet, are the first full peer-reviewed efficacy results to be published for a COVID-19 vaccine.

Developed in cooperation with AstraZeneca, the Oxford COVID-19 vaccine uses a chimpanzee adenovirus viral vector that cannot cause disease in humans and expresses the SARS-CoV-2 spike protein. This means the vaccine delivers the spike protein genetic code into vaccinated people’s cells, which then produce the protein, teaching the immune system to recognise and attack the virus. Past trial results have found that the vaccine induces antibody and T cell immune responses and is safe in adults aged 18 years and over, including older adults.

“We have known for many years that adenoviral vectored vaccines fulfil the requirements for use against outbreak or pandemic diseases,” said Professor Sarah Gilbert from the University of Oxford. “They are safe, highly immunogenic, can be manufactured in large quantities at low cost and do not require frozen storage.”

For the new study, the authors analysed data from 23,745 adults in the UK, Brazil and South Africa. Half of the participants were given the COVID-19 vaccine and the other half were given a control (either a meningococcal conjugate vaccine or saline). The trial was originally designed to assess a single dose of the vaccine, but following review of the immune response data in the UK Phase 1/2 study (which found a second dose boosted immune responses), another dose was added to the trial protocol.

Participants in the COVID-19 vaccine group received two doses each containing 5x1010 viral particles (a standard dose). However, a subset (1367 people) in the UK received a half dose as their first dose, followed by a full second dose. This was because of differences in the results of quantification methods between batches of the vaccine. The low-dose/standard-dose group did not include adults over the age of 55 years as the low dose was given in an early stage of the trial before recruitment of older adults had commenced.

The vaccine was found to be safe, with only three out of 23,745 participants over a median of 3.4 months experiencing serious adverse events that were possibly related to a vaccine; one in the vaccine arm, one in the control arm and one in a participant who remains masked to group allocation. These participants have recovered or are recovering, and remain in the trial. Safety monitoring of all participants continues.

The primary outcome of the study was to determine how many cases of symptomatic COVID-19 disease there were in participants who had received two doses of the vaccine, compared with controls; only cases that occurred at least 14 days after the second vaccination had been given were included. Of 11,636 eligible participants, there were 131 cases of symptomatic COVID-19 disease more than 14 days after the second vaccine dose. This included 30/5807 (0.5%) cases in the vaccine group and 101/5829 (1.7%) cases in the control group, which equates to a vaccine efficacy of 70%.

When breaking this down based on vaccine dose, those who received two standard doses of the vaccine saw a vaccine efficacy of 62%, based on 27/4440 (0.6%) cases in the vaccine group and 71/4455 (1.6%) cases in the control group. The low-dose/standard-dose group vaccine efficacy was 90%, based on 3/1367 (0.2%) cases in the vaccine group and 30/1374 (2.2%) cases in the control group.

The authors completed exploratory subgroup analyses at the request of peer-reviewers to study the difference in efficacy against symptomatic disease in the low-dose/standard-dose group and two standard doses group. These were to help understand whether the difference was related to the dose or other factors. They found that, irrespective of age or time between doses, their analyses suggested higher efficacy in the low-dose/standard-dose group. However, these exploratory analyses will require further research as more data becomes available from the trial.

Five cases of symptomatic COVID-19 disease occurred in people aged over 55 years old, but vaccine efficacy in older age groups could not be assessed as there were too few cases. The authors say that this analysis will be completed in future.

“In order to assess vaccine efficacy, we need to have a sufficient number of COVID-19 cases among participants to indicate that the vaccine is protecting them from disease,” said study author Dr Merryn Voysey, from the University of Oxford. “Since recruitment of older adults started later than in younger adults there has been less follow-up time for these cohorts and less time to accrue COVID-19 cases. This means we have to wait longer to have sufficient data to provide good vaccine efficacy estimates in smaller subgroups.”

The trial also measured protection against asymptomatic infection by asking 6638 UK participants to complete weekly COVID tests; however, it is important to note these data are secondary outcomes and findings need to be confirmed when there is more data available from the trial. There were 69 cases of asymptomatic COVID-19 disease identified in the weekly testing — including 29/3288 (0.9%) cases in the vaccine group and 40/3350 (1.2%) cases in the control group — leading to a vaccine efficacy against asymptomatic transmission of 27%.

In the low-dose/standard-dose group, there were 7/1120 (0.6%) cases in the vaccine group and 17/1127 (1.5%) cases in the control group, resulting in a vaccine efficacy against asymptomatic transmission of 59%. In people given two standard doses, there were 22/2168 (1%) cases in the vaccine group and 23/2223 (1%) in the control group, which equates to a vaccine efficacy against asymptomatic transmission of 4%.

The authors note that they are not yet able to assess duration of protection, as the first trials were initiated in April 2020 and all disease episodes have accrued within six months of the first dose being administered. Further evidence will be required to determine duration of protection and the need for additional booster doses of vaccine.

“The results presented in this report provide the key findings from our first interim analysis,” Dr Voysey said. “In future analyses, with more data included as it becomes available, we will investigate differences in key subgroups such as older adults, various ethnicities, doses, timing of booster vaccines, and we will determine which immune responses equate to protection from infection or disease.”

AstraZeneca is now seeking Emergency Use Listing from the World Health Organization for an accelerated pathway to vaccine availability in low-income countries, and is engaging with governments, multilateral organisations and collaborators around the world to ensure broad and equitable access to the vaccine at no profit for the duration of the pandemic. The company claims to have the capacity to manufacture up to 3 billion doses of the vaccine in 2021 on a rolling basis, pending regulatory approval.

“Today’s peer-reviewed publication enables a full disclosure of the Oxford program interim analysis,” added AstraZeneca CEO Pascal Soriot. “The results show that the vaccine is effective against COVID-19, with in particular no severe infections and no hospitalisations in the vaccine group, as well as safe and well tolerated. We have begun submitting data to regulatory authorities around the world for early approval and our global supply chains are up and running, ready to quickly begin delivering hundreds of millions of doses on a global scale at no profit.”

Image credit: ©stock.adobe.com/au/yurolaitsalbert

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