How does the Oxford/AstraZeneca vaccine work?


When news broke that a vaccine against Covid-19 developed by Oxford university and AstraZeneca had received approval from the UK’s medicines regulator, it offered an instance of unalloyed triumph for a government that has been widely criticised for its handling of the pandemic.

Matt Hancock, the health secretary, hailed it as “a moment to celebrate British innovation” and highlighted the prospective boon to low income countries, which will benefit from the vaccine’s cheapness and portability.

But questions remain about whether the vaccine can be rolled out fast enough to check the UK’s soaring Covid infection rates, and how quickly it can be deployed by the rest of the world.

Why the vaccines vary

The currently approved Covid-19 vaccines all work by injecting genetic code for the “spike protein”, which the Sars-Cov-2 coronavirus uses to infect people. After vaccination the recipients’ cells translate the genes into protein, which primes the immune system to recognise and attack the virus if they are subsequently exposed to infection.

The Oxford/AstraZeneca vaccine delivers the genes in a genetically engineered “viral vector” — a weakened version of a harmless adenovirus originating in chimpanzees. Several other Covid-19 vaccines use viral vectors, including those developed by Russia’s Gamaleya Research Institute, China’s CanSino and Johnson & Johnson of the US.

Chart of number of confirmed vaccine doses, by region (m) which shows the Oxford/AstraZeneca vaccine  at the top with nearly 2.5bn doses

By contrast, the approved vaccines from BioNTech/Pfizer and Moderna inject spike protein genes that are very similar to those in the viral vector jabs but encapsulate the genetic material — messenger RNA or mRNA — in microscopic oily droplets called lipid nanoparticles.

A key advantage of adenovirus technology is that the spike protein genes are more stable when incorporated into a viral vector than in a lipid nanoparticle. This stability enables the Oxford/AstraZeneca vaccine to be stored at fridge temperature while the mRNA products require deep freezing. Viral vector vaccines also cost less to manufacture.

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How safe are you after a single dose?

The vaccine is given in two doses, between one and three months apart. The relatively long period between jabs will allow manufacturers to replenish supplies, meaning health officials will not have to set aside enough to give a second dose. This should allow the UK to quickly increase the number of people it vaccinates.

According to Oxford and AstraZeneca, the efficacy after a single dose was about 70 per cent — although this is significantly lower than achieved with two doses of BioNTech and Moderna vaccines. The second dose was needed to increase the duration of that protection, they said.

Andrew Pollard, chief investigator on the Oxford programme, said in the UK arm of the vaccine trial, people had received two doses four weeks apart “and some up to 12 weeks apart and some even longer than that”. Other trials in Brazil and South Africa had slightly shorter periods between the two doses.

Putting the data together from each trial had provided “good evidence of protection right from four weeks through to 12 weeks, which is the data the MHRA has scrutinised in great detail”, Prof Pollard added.

What impact will approval have on the UK programme?

The Oxford/AstraZeneca vaccine can be stored at normal fridge temperatures and GPs say the less demanding storage conditions will allow far more family doctors to participate in the programme. Many have opted out of delivering the BioNTech vaccine as their premises are not equipped to administer the vaccine safely.

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Care homes have also in many cases lacked the facilities or numbers to deploy the BioNTech vaccine, which arrives in batches of 975 doses. They will also find the Oxford vaccine easier to administer.

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Martin Marshall, who heads the Royal College of GPs, the professional body, said GPs and their teams were already “overcoming huge logistical challenges” to deliver the BioNTech/Pfizer vaccine. The Oxford/AZ jab “will overcome many of those challenges as it is much more like other vaccines already delivered in general practice, making it easier for GPs, our teams and other primary care professionals to store it appropriately, and ultimately vaccinate a greater number of patients, at a faster pace in the community”, Prof Marshall added.

Pharmacists are expected to play a far bigger role in the programme now that the Oxford/AstraZeneca vaccine has been approved. Earlier this month the National Pharmacy Association said they “may be especially important in achieving uptake in poorer communities, because of the generally high level of access to pharmacies in deprived neighbourhoods”.

Asked whether any of the vaccine supplies would be available for private purchase, AstraZeneca said that in the UK — the only country which has so far approved the vaccine — “our agreement to supply vaccine was made directly with the UK government. The entirety of the vaccines we are producing for the UK market will be going directly to them.”

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What does this mean for other countries?

It is likely to be a while before other major western medicines regulators follow the UK lead in approving the vaccine. The European Medicines Agency and the US Food and Drug Administration have both made clear that more data is needed.

The European Medicines Agency said that it has not received sufficient data to give the Oxford/AstraZeneca vaccine a conditional authorisation, adding that approval in January was unlikely.

FDA approval is not expected until later next year, as a late-stage trial is still under way in the US.

Pie chart of share of vaccine supply in low- and middle-income countries (%) that shows the Oxford/AstraZeneca vaccine is crucial to low- and middle-income countries - it is nearly 44% of supplies

Mene Pangalos, head of Biopharmaceuticals R&D for AstraZeneca, said the company was “answering all the questions [the EMA] have asked and working very collaboratively with them and the same is true for the FDA. I feel confident that over the coming weeks we will get additional approvals around the world.”

The UK approval could be a game-changer for poorer countries, however. As part of its collaboration with Oxford university, AstraZeneca pledged to make the vaccine available at cost to the developing world in perpetuity.

The World Health Organization said it welcomed the approval because “of the delivery attributes, the potential scale and affordability” of the vaccine.

However, the UK’s announcement is independent of the health body’s prequalification process, which streamlines regulatory approval for countries that do not have the means to carry out clinical assessment and makes vaccines available for procurement to lower-income nations through Unicef and the Pan American Health Organization.



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