How the Oxford-AstraZeneca vaccine works and why it matters

AstraZeneca and Oxford university announced on Monday that the coronavirus vaccine they were developing together was up to 90 per cent effective depending on dosage. It is the third vaccine candidate to give positive results in large-scale phase 3 trials and, while it is not as effective as the other two, it is being offered at a much lower price and is easier to transport and store.

How impressive are these results? 

Until early November, the average efficacy found in the Oxford/AstraZeneca vaccine of 70 per cent — and close to 90 per cent if the first shot is a lower dose than the second — would have been regarded as a triumph. Regulators and many scientists would have been happy with any vaccine that was more than 50 per cent effective.

Two other vaccine candidates using different technology, made by Moderna and the Pfizer/BioNTech partnership, have raised the bar considerably within the past two weeks. Each reported around 95 per cent efficacy in phase 3 clinical trials. However, independent experts say people should not leap to conclusions on the basis of what are still interim findings. 

Charlie Weller, head of vaccines at Wellcome, said: “The preliminary results from the Oxford/AstraZeneca team are hugely encouraging. They suggest that it is highly effective in protecting against serious illness and it may reduce transmission.” 

No one who received the Oxford vaccine required hospitalisation with Covid-19 symptoms. There was also evidence that it reduced asymptomatic infection.

How does the Oxford/AstraZeneca vaccine work? 

It is based on a harmless adenovirus from a chimpanzee, which has been engineered in the lab to include genes from Sars-Cov-2, the coronavirus that causes Covid-19. When the genetically modified adenovirus is injected into human cells, they make coronavirus proteins that prime the immune system to respond to future infections with Sars-Cov-2.

Several other Covid-19 vaccines in development, including the Russian Sputnik-V and candidates from Johnson & Johnson of the US and CanSino of China, use adenoviruses.

In contrast, the Moderna and Pfizer/BioNTech vaccines use mRNA technology, which carries Sars-Cov-2 genes into cells in microscopic droplets of oily lipid rather than in another virus.

Why does the dosing regime make such a difference in the Oxford/AstraZeneca vaccine? 

Sarah Gilbert, Oxford professor of vaccinology, said the team had been keen to experiment with lower doses but had not expected the combination of a half dose followed by a full dose to boost performance so dramatically — giving 90 per cent efficacy, compared with 62 per cent for two full doses.

The reasons for this improvement will remain speculative until more research has been done. The Oxford team says one likely explanation is that a smaller dose is a better initial primer of the immune system, though no licensed vaccine has a low first dose followed by a higher second dose.

How easy would it be to distribute this vaccine?

Vaccines require “cold chains” to keep their active ingredients intact and stable while they reach patients. That is a huge challenge because large parts of the world lack the infrastructure to do this.

The Oxford/AstraZeneca vaccine can be kept long term at 2C to 8C, the temperature of a conventional fridge. For comparison, the mRNA vaccines developed by Pfizer/BioNTech and Moderna require much lower temperatures of minus 70C and minus 20C respectively.

Public health professionals have warned of the challenges of building worldwide distribution networks at a time of squeezed budgets around the world, though organisations such as Unicef are stepping up their efforts to make sure poorer nations have cold chains in place. 

Is this good news for poorer nations?

Yes. AstraZeneca has pledged to sell the vaccine at cost, eschewing profits, for the duration of the pandemic. It is priced at about $3 to $4 per dose — much less than other vaccine candidates. Its ease of distribution also helps.

At least one manufacturing agreement shows that the company could call an end to the pandemic as soon as July next year and move to commercial pricing. But AstraZeneca has said it will seek expert guidance on when to do so and that it will always sell the vaccine at cost to poorer nations.

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Other vaccines under development are priced for profit and much of their supply has been reserved by richer countries. Johnson & Johnson, which is expected to release phase 3 results early next year, has also said it will sell its vaccine at cost during the pandemic.

Professor Andrew Pollard, director of the Oxford Vaccine Group, said this was “a vaccine for the world” but Germany’s chancellor Angela Merkel said at the weekend that she was “concerned” about supply for poorer countries, citing the lack of negotiations between drug companies and Covax, an international vaccine initiative.

What does it mean for AstraZeneca?

The company had no vaccines business before the Oxford collaboration and has said it does not expect the jab to affect its accounts.

On Monday, London-listed shares in the drugmaker fell 3.5 per cent. Analysts said this was partly because the average efficacy figures were lower than those reported by competitors.

“In reality, if the vaccine is 70 per cent effective, that’s absolutely fine. It’s the most accessible of all the vaccines and so will still be used widely if approved,” said Shore Capital’s Adam Barker.

Emily Field of Barclays said investor focus would return to innovative research areas, where Astra “continues to offer one of the best earnings growth rates across Europe”.

Additional reporting by Michael Peel in Brussels

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