Why bad news for AstraZeneca’s vaccine is a roadblock on the way out of the pandemic

It’s the news that many feared: early data shows the Oxford-AstraZeneca vaccine may provide only “minimal protection” against mild to moderate illness caused by the coronavirus variant first identified in South Africa.

But this doesn’t mean governments should throw out their AstraZeneca stockpiles. Experts say it’s possible – and very likely – that the shot is still effective in preventing severe disease and death.

The news could, however, be a major roadblock on the world’s way out of the pandemic, which can’t “end” until the virus stops circulating widely.

The Oxford-AstraZeneca vaccine is cheaper and easier to transport and store than some of the other vaccines approved for use to date and as such, was going to play a key part in combating the pandemic in low and middle-income countries. If the vaccine isn’t effective enough against the new variant, it could deepen the already huge vaccination gap between the world’s richest and poorest countries.

FILE - In this Wednesday, June 24, 2020 file photo, a volunteer receives an injection at the Chris Hani Baragwanath hospital in Soweto, Johannesburg, as part of Africa's first participation in a COVID-19 vaccine trial developed at the University of Oxford in Britain in conjunction with the pharmaceutical company AstraZeneca. On Friday, Oct. 23, 2020, AstraZeneca Inc. announced that the Food and Drug Administration is letting it resume testing of its COVID-19 vaccine candidate in the U.S. (Siphiwe Sibeko/Pool via AP)

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The study from South Africa suggested that two doses of the AstraZeneca vaccine provided “substantially reduced” protection against mild to moderate Covid-19 disease from the new virus variant first identified there, known as B.1.351.

The study has not yet been peer reviewed or published in full, so many unknowns remain. What we do know is that it included a relatively small number of volunteers who were predominantly young and healthy and therefore not likely to suffer from severe Covid-19 disease. That meant the study did not assess protection against severe disease, hospitalization and death and many experts have suggested it could still prevent these outcomes.

“In the medium term, what matters most is preventing more serious forms of Covid-19; and it is thought the AstraZeneca vaccine will do this,” Dr Peter English, a consultant in communicable disease control, told the UK’s Science Media Centre.

New vaccination strategy

Less effective vaccines could force countries where the new variants become dominant to shift their vaccination strategy.

Instead of trying to achieve herd immunity, the focus might be on preventing as many deaths as possible even while the virus continues to circulate.

South Africa is pausing its rollout of the AstraZeneca vaccine following the release of the study on Sunday.

Speaking to CNN, Professor Salim Abdool Karim, who is a co-chair of South Africa’s Covid-19 advisory committee, said the country will likely adopt a more “stepped approach,” in which they assess the impact of the vaccine as it is rolled out.

“We would start by vaccinating about 100,000 individuals in the first step. We would look at the hospitalization rates once we’ve done those vaccinations. And if we find that the hospitalization rates are below the threshold – that we are looking at – then we can be confident that the vaccine is efficacious … and if so, we can then proceed to continuing the rollout,” he said.

“If we find that the hospitalizations are substantial – more than we anticipated – then we would have to stop, take stock of where we are and perhaps switch to other vaccines.”

Critical Care staff carry out a tracheostomy procedure on a Covid-19 patient on the Christine Brown ward at King's College Hospital in London on January 27, 2021.

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But the AstraZeneca vaccine is a key part of mass vaccination programs in many countries worldwide.

The UK has been administering it since last month and the government said Monday it would continue to be used. While the UK is one of the at least 41 countries where the South African variant had been detected, the number of cases caused by it remain extremely low. But the mutation found in the South African variant – known as the E484 mutation – has also been found independently in a samples of the variant first seen in the UK.

The European Union has also approved the vaccine, although several European countries have advised against using it in older people because of limited efficacy data in that age group.

The COVAX program – a coalition that includes Gavi and the World Health Organization with the aim of distributing Covid-19 vaccines to poorer countries – is reliant on this vaccine. Last week, COVAX announced a plan to distribute more than 337 million doses worldwide – of which 336 million doses are the AstraZeneca-Oxford vaccine and 1.2 million doses are the Pfizer-BioNTech vaccine.

Experts from COVAX said Monday that the WHO’s Strategic Advisory Group of Experts is finalizing new recommendations for use of the AstraZeneca vaccine and will present them to the Director-General on Tuesday.

Other coronavirus vaccines have shown more promise against the new variants. Real-world trials of some of the other vaccines, including Johnson & Johnson and Novavax, showed some protection against the new variants. Pfizer-BioNTech and Moderna also said their vaccines should be effective against the new variants, although their data was based on lab studies rather than real-world trials.

South African health officials said they are hoping to receive first doses of the Johnson & Johnson vaccine by the end of the week. The country has also ordered another 20 million vaccines through a deal with Pfizer/BioNTech, but it is not clear when those doses will arrive.

Still, the AstraZeneca vaccine will be, at least initially, the most accessible option for many countries.

Relieving the burden on health services

A vaccine’s role is to teach the immune system to spot and fight a virus quickly. Essentially, it helps the body remember an infection so it acts faster if you become infected. “Your own immune system will also react to clear the virus, but without the vaccine, this reaction will be slower,” said Dr Julian Tang, honorary associate professor and clinical virologist at the University of Leicester.

The currently available coronavirus vaccines work by inducing antibodies and T-cells that have been shown to fight the original coronavirus. Antibodies work by attaching to and attacking the proteins on the surface of the virus – in the case of coronavirus, this is the spike protein.

If the virus changes too much, notably in its spike protein, the antibodies induced by the vaccine may not not bind to the new version of the virus very well, Tang explained.

“This means that these vaccine antibodies cannot clear as much of these viruses when you are infected so there is more virus left that needs to be cleared by your own immune response – which reacts more slowly,” he added.

A patient receives an injection of the Oxford/AstraZeneca Covid-19 vaccine at the vaccination centre set up in Brighton, southern England

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“But the studies suggest that there is enough binding from these vaccine antibodies to at least remove some of the variant viruses from the system – to prevent more severe disease and death.”

One of the main reasons the pandemic has been deadly is because of the sheer number of people in need of medical attention, and a partially effective vaccine, while not ideal, would reduce this burden.

There have been instances where health care systems became unable to cope with the number of patients coming in. When this happens, some patients might die because they can’t access help on time. There is also a knock-on effect on the entire system, with non-urgent treatments postponed or canceled.

Experts argue that a vaccine will prove to be beneficial if it can reduce the burden on health services.

“This may look like fewer individuals requiring an ICU bed and more individuals able to recover at home,” said Dr. Oliver Watson, an infectious diseases researcher at Imperial College London, adding that this could have “real material consequences in settings where hospitals are very stretched.”

This has been the case in many European countries, including the UK, where the government was forced to open several field hospitals to prevent the National Health System becomes overwhelmed.

Tweaking the vaccine

The data from South Africa is no doubt a setback to vaccination campaigns but scientists are already working on updates to the existing vaccines to make them more effective against new variants.

AstraZeneca said Saturday it is working with Oxford University to adapt the vaccine against the B.1.351 variant and that it would advance it through clinical development to make it “ready for autumn delivery should it be needed.” Last month, Pfizer said it was “laying the groundwork” to create a vaccine booster that could respond to coronavirus variants.

“We see this all the time with the influenza vaccine,” said Tang. Flu vaccines are adapted each year to target the virus strains that are circulating the most. Sometimes, the vaccine picked doesn’t match the strain that becomes prevalent.

“Mismatched vaccine seasons do allow more influenza infections, morbidity and mortality – but to some extent, this is inevitable as the virus will always be mutating first – then we will have to adjust our vaccines to match the new virus,” Tang added.

The UK Health Secretary Matt Hancock said Monday the flu blueprint might work for the coronavirus in the future.

“The jab is updated each year according to the mutations and variations that have happened and been spotted in the preceding few months, and that is manufactured over the summer, and then delivered into the arms of those who are most vulnerable to flu in the autumn,” he said.

When it comes to Covid-19, he explained that we need to be thinking about how to protect people in a similar way.

The good news is that developing a vaccine that would work against the new variants doesn’t mean starting from scratch, so updates could become available soon.

“The genome of the variant spike protein is known, and the technology to “plug in” the genes for it into mRNA and vector vaccines is well-established,” said English. “Within months we hope to see availability of new vaccines, tailored to the South African variant.”