At the very end of December, UK healthcare regulator the Medicines and Healthcare Products Regulatory Agency (MHRA) approved a second Covid-19 vaccine for emergency use in adults. The vaccine in question is AstraZeneca (AZ) and the University of Oxford’s two-dose adenovirus vaccine candidate. This approval occurs in the context of an escalating Covid-19 crisis in the UK. To date, there have been 2.7m cases of Covid-19 in the UK and more than 75,000 people have tragically died of the viral disease.
The MHRA began its rolling review of the AZ/Oxford Covid-19 vaccine in September and the emergency approval is based on a Phase III programme led by the University of Oxford. Interim results published in The Lancet in early December showed that the vaccine was both safe and effective at preventing symptomatic Covid-19, and particularly at protecting against severe disease and hospitalisation.
“The approval of the Oxford vaccine is a massive step forward in our fight against coronavirus,” said Secretary of State for Health and Social Care Matt Hancock. “It is a tribute to the incredible UK scientists at Oxford University and AstraZeneca, whose breakthrough will help to save lives around the world. The light at the end of the tunnel just got brighter.
“Vaccines are the exit route from the pandemic. We have already vaccinated hundreds of thousands of vulnerable people and the new Oxford jab will allow us to accelerate our vaccination plan, allowing us to return to normality in the future.
“I want to thank every single person who has been part of this British success story. While it is a time to be hopeful, it is so vital everyone continues to play their part to drive down infections.”
This is good news, it significantly increases supply and flexibility of vaccines to combat COVID in the UK and internationally. Many thanks to the scientists, research funders (including NIHR), research clinical staff and above all the many volunteers who took part in the trials. https://t.co/QzF3aRzKIZ
— Professor Chris Whitty (@CMO_England) December 30, 2020
Chief investigator of the Oxford Vaccine Trial and director of the Oxford Vaccine Group Professor Andrew Pollard added: “The regulator’s assessment that this is a safe and effective vaccine is a landmark moment, and an endorsement of the huge effort from a devoted international team of researchers and our dedicated trial participants. Though this is just the beginning, we will start to get ahead of the pandemic, protect health and economies when the vulnerable are vaccinated everywhere, as many as possible as soon as possible.”
UK rollout of AstraZeneca/Oxford vaccine begins
Just five days after the approval, on Monday 4 January, the UK began rolling out the AZ/Oxford vaccine. One of the first people to receive the vaccine was Professor Pollard.
The approval of the AZ/Oxford vaccine by the MHRA significantly speeds up the UK’s Covid-19 vaccination strategy. The country has secured access to 100 million doses of this vaccine through its Vaccines Taskforce, compared to 40 million doses for the other approved Covid-19 vaccine, Pfizer/BioNTech’s BNT162b2. Half a million of the AstraZeneca/Oxford doses were already available on Monday, with tens of millions expected to be delivered in the coming weeks and months.
In addition, the AZ/Oxford vaccine does not present the same logistical challenges associated with ultra-low temperature storage that the Pfizer/BioNTech vaccine requires. Instead, the AZ/Oxford vaccine can be stored at normal fridge temperatures, making it easier to quickly transport straight to GP practices and care homes and therefore speeding up vaccination programmes. This was noted by England’s deputy chief medical officer Professor Jonathan Van-Tam in a statement.
This aspect of the AZ/Oxford vaccine, as well as its low cost of around $3 per dose, is central to why this vaccine is seen as promising for tackling not only the UK’s Covid-19 epidemic, but for helping to end the pandemic globally.
Issues facing the UK vaccine rollout
Although the MHRA’s emergency approval of the AstraZeneca/Oxford vaccine has been greeted with optimism by the public and scientific community, some concerns remain about the specifics of the government’s vaccination strategy.
The MHRA and the Joint Committee on Vaccinations and Immunisation (JCVI) have decided that the AstraZeneca/Oxford vaccine will be administered through two doses with the second being administered between four and 12 weeks after the first. The MHRA has also amended its strategy for the Pfizer/BioNTech Covid-19 vaccine from three weeks between doses to up to 12 weeks. The aim of this approach is to use the doses available as effectively as possible.
Among the questions Francis Crick Institute Retrovirus-Host Interactions Laboratory group leader Dr Jonathan Stoye asked about the AstraZeneca/Oxford vaccine is “what do we really know about the dosing schedules?”
Stoye continued: “If the original study design called for a four-week interval between first and second doses, how much firm information do we have about varying this time? Is there flexibility to extend this period beyond 12 weeks?”
University of Reading associate professor in cellular microbiology Dr Simon Clarke added: “The conditions for use allow the second dose of the vaccine up to 12 weeks after the first, with some protection being provided from 22 days. It remains unclear exactly how much protection is offered, and the regulators are using unpublished data to come to their judgement.
“At a time of increasing rates of infection, hospitalisation and death from Covid-19, greater clarity is urgently needed over any risks associated with extending the second dose window to 12 weeks,” continued Clarke. “It would be deeply unfortunate to increase the risk of vulnerable people so that low-risk individuals can receive their first dose of the vaccine.”
However, some experts have defended the decision. For instance, Professor Paul Hunter of the University of East Anglia’s Norwich Medical School stated: “In my view the evidence for delaying the second dose of vaccine to enable as many as people as possible to receive the first dose sooner is clear”. He cites data from papers published in the New England Journal of Medicine, The Lancet and Nature.
“So I welcome the news that second doses will be delayed to enable more people to have their first dose sooner and with the rapidly spreading new variant, I have no doubt this decision will save many lives.”
Other challenges surrounding the rollout of the AZ/Oxford vaccine include issues in gaining access to quality-controlled and safety-checked batches. Although attempts have been made over the past year to secure supply chains and manufacturing capacity for Covid-19 vaccines, the Financial Times reported that the availability of supplies have been slowed by MHRA’s protocols and the AZ’s inability to build up buffer stocks in advance of the launch.
This situation, however, should become less problematic as the UK progresses from its initial approval. Hope remains that the country may be able to achieve its target of vaccinating two million people a week with one of the approved Covid-19 vaccines by the end of January.