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How does the Oxford & AstraZeneca COVID-19 vaccine work? A guide to viral vector vaccines

Infographic on viral vector vaccines. The SARS-CoV-2 virus contains a gene which codes for the virus spike protein. In viral vector vaccines, this gene is added to the genetic material of another virus, making it a viral vector. This vector is altered so it can't cause disease. Once the viral vector is inside our cells it produces the virus spike protein, triggering an immune response. These vaccines can be produced relatively quickly. The genetic instructions for making the spike protein are broken down in our cells after use. Viral vector vaccines cause a strong immune response which can mean minor side effects are more common. Different viruses can be used as viral vectors; the AstraZeneca vaccine uses a chimp adenovirus, while some others use a human adenovirus. Some people may have immunity to human adenoviruses, potentially reducing vaccine effectiveness.
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Relatively hot on the heels of the Pfizer & BioNTech RNA vaccine, today the UK has approved the Oxford University & AstraZeneca COVID-19 vaccine. The Oxford vaccine is a viral vector vaccine, which works slightly differently to the RNA vaccines. This graphic, made with the Royal Society of Chemistry, looks at how they work and highlights other vaccines of this type in use or development for COVID-19.

Some of the groundwork necessary to produce these vaccines is similar to that for the RNA vaccines we examined previously. As with those vaccines, we need to know the genetic code for the virus first. In particular, we need to know the code for virus proteins. Like the RNA vaccines, the viral vector vaccines make use of the code for the virus spike protein. This is the protein the virus uses to penetrate cells and kick off an infection.

RNA vaccines deliver the RNA directly to our cells, encapsulated in tiny fat droplets to protect it. The challenge with this approach has been well-documented: the vaccine must be stored at low temperatures to keep the RNA stable. This may make it harder to distribute and use these vaccines in some countries.

The viral vector vaccines get around this problem by smuggling the virus protein RNA into our cells in a different way. Scientists can add the RNA to the genetic material of another virus, a viral vector, which is then used in the vaccine.

As with the RNA vaccines, once the virus protein RNA is in our cells, our cellular machinery uses it as a blueprint to make the virus protein. This then causes an immune response, which trains our body’s immune system to recognise the SARS-CoV-2 virus. If we’re subsequently infected, our immune system will realise it’s seen part of this virus before, and marshall our immune response more quickly.

You might worry about the idea of smuggling in the SARS-CoV-2 virus RNA inside another virus. Isn’t there a risk that these viral vectors could themselves cause an infection? To avoid this risk, scientists use genetically altered viral vectors which can’t cause disease. The RNA which produces the SARS-CoV-2 spike protein is also broken down once our cells have made the protein, so this, too, poses no infection risk.

Vaccines can use several different viruses as viral vectors, but the most common amongst the COVID-19 vaccine candidates are adenoviruses. Adenoviruses are amongst the selection of viruses which can cause the common cold. It’s estimated that they cause a little under 5% of these infections.

Some of the COVID-19 vaccine candidates use human adenovirus viral vectors. This includes the Russian Sputnik V vaccine and the Chinese CanSino Biologics vaccine. One potential issue with these vectors is that, inevitably, some of us will have been exposed to these viruses before. Because of this, we may have some degree of immunity to them. This means the viral vector itself produces an immune response, which may mean that the immune response to the SARS-CoV-2 virus isn’t boosted as effectively.

The Oxford vaccine avoids these issues by using a chimp adenovirus instead. Far fewer people will have an existing immune response to the chimp adenovirus, so we can be confident that it won’t impact our immune response to the vaccine. Another vaccine in development in Italy has used a similar approach with a gorilla adenovirus.

All the viral vector vaccine candidates for COVID-19 are non-replicating. This means that they don’t create additional viral vectors in the cells that they infect. Though they need higher doses than replicating viral vector vaccines, it also adds to our confidence in their safety.

So if you get given the Oxford vaccine, what can you expect? Well, we know that viral vector vaccines cause a strong immune response. This can mean that the minor side effects of headaches and fever after taking the vaccine may be more common. But this is a positive sign that the vaccine is working, so isn’t a cause for concern.

The Oxford vaccine’s approval is undoubtedly good news. It’s important to remember, though, that the vaccination programme will take time. It’s not a “get out of jail free” card for the current wave of COVID-19 cases, and the weeks and months ahead will still be incredibly challenging, but it will hopefully help blunt COVID’s threat later in 2021.

This graphic was developed in partnership with the Royal Society of Chemistry.

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