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Sarah Gilbert on how her team is making the Oxford coronavirus vaccine

Sarah Gilbert, head scientist on the Oxford vaccine for covid-19 explains why we have reason to be hopeful and what her life is like right now
Sarah Gilbert is professor of vaccinology at the University of Oxford, leading its research on flu vaccines and emerging pathogens
Photos by John Cairns

Last week was a big one for Sarah Gilbert at the University of Oxford, leader of the team that created the “Oxford vaccine”, a front runner in the race for a coronavirus vaccine. On 20 July, her team published results showing that the vaccine produces the desired immune responses in people.

Gilbert says she took a moment to pause ahead of the announcement – she had most of the day before, a Sunday, off.

That is a rare luxury these days. She normally works long hours, including on weekends. “There is a lot going on during the week, so weekends are a time to catch up on more substantial pieces of work with fewer interruptions,” she says.

Gilbert gradually moved into vaccine development after joining Oxford in 1994. Even so, she never imagined working on a vaccine to tackle a massive global pandemic. “We had been starting to prepare for a ‘disease X’ vaccine, but that was always envisaged as a novel pathogen that would cause an outbreak rather than a pandemic.”

The type of vaccine she has been working on against coronavirus is known as a viral vector vaccine. The key component is DNA coding for a surface protein – which would normally trigger an immune response – from the virus you want to protect against.

Like a Trojan Horse, this is put inside the shell of an adenovirus that causes colds in chimpanzees, which delivers it to human cells, where the protein is made.

In response, the body produces both antibodies that circulate in the blood and bind to any matching viruses they encounter, and T-cells that destroy infected cells before they make more virus.

To create the coronavirus vaccine, which is being developed in collaboration with drugs firm AstraZeneca, the researchers simply had to put DNA coding for the virus’s surface protein into the adenovirus “cassette” they had already created for other vaccines.

That meant they could produce small batches of the vaccine for initial tests in just weeks. It can take several years to get to this point in vaccine development.

A chimp adenovirus shell is used instead of a human one because it doesn’t get mopped up by our immune system before delivering its cargo. “Vaccines based on human adenoviruses don’t work quite so well in people who have some immunity to the adenovirus,” says Gilbert.

So far, things look good. The results published last week show that the Oxford vaccine produces good antibody and T-cell responses after two doses and only minor side effects, including pain at the injection site, tiredness, aches and fever in some cases.

The big question is whether it really protects people from infection. To find out requires phase III trials in which thousands of people are given either the vaccine or a placebo. They aren’t told which, so they don’t change their behaviour. These trials are now under way.

If the vaccine works, fewer people given it should end up catching the coronavirus compared with those who got the placebo. Ideally, there would be no cases at all among those vaccinated, but even a vaccine that provides only partial protection would be better than nothing.

“We all want the best vaccine we can get, but will accept one that is safe, despite some tolerable side effects immediately after vaccination, and reduces mortality,” says Gilbert. “There aren’t any vaccines against coronaviruses that infect humans, so there is nothing to compare with.”

Normally, human trials of vaccines take a decade or more. “The reasons for being slow usually are financial,” says Gilbert.

If all goes well, the Oxford vaccine might get the go-ahead from regulators this year. This would be an amazing achievement, but Gilbert thinks we might have done even better. “We could have been quicker to get started if we had been better prepared. We need more investment in pandemic preparedness to do better next time.”

One of the biggest worries around the promise of a vaccine to end the pandemic is that our immune response to the virus might only provide short-lived protection. However, that issue doesn’t necessarily translate to vaccines, says Gilbert. “Immunity to pathogens and vaccines is not necessarily the same,” she says. “The vaccine may provide longer‑lived immunity.” Fears of decreasing immunity after infection are probably overstated too, she says: “It’s usual for antibodies to reach a peak level and then decline over time.”

Once we have one or more effective vaccines, Gilbert thinks it should be given first to healthcare workers, both to protect them and to prevent transmission within hospitals and care homes. “That is where the vaccine can have most impact,” she says.

The hope of many is that normal life can resume once a vaccine is available, but this will take time. “It won’t be available to everyone at the same time and the vaccine may not work very well in older people. If that is the case, we need the rest of the population to be vaccinated to prevent transmission and protect the vulnerable.”

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Topics: coronavirus / covid-19 / Vaccines