Andrew Pollard: How do vaccines work?

Andrew Pollard has played a pivotal role in the development of numerous vaccines across his career, including those for typhoid, meningitis, influenza and Ebola. Here he gives us a rundown of how they work...

Chris – That’s quite a CV. Why did you end up going down the infectious diseases route and the vaccine route in the first place?

Andrew – Well, I actually got into the vaccine route later. I started off really interested in the immune system, and particularly the immune system of children. If you go back 250, 300 years, half of all children died during childhood before the age of 15. One in two children died. Most of those died from infectious diseases. So there’s no world in which having lots of bad things happen to you and surviving them is the right thing to do.

You really need to have an environment around children that protects them from these life-threatening illnesses. We’ve achieved that through public health since really the mid-1800s, when acts around clean water and air pollution started to appear, which then started a trend of plummeting under-five mortality in this country. That really was completed by the advent of vaccines, on a large scale, in the 20th century.

Chris – Do we have any insights, then, into roughly what the scale of morbidity and mortality is that are being prevented by vaccines? How game-changing have they really been worldwide?

Andrew – Well, if we think about the annual lives saved in childhood from the global vaccine programmes, which are not as comprehensive as ours here, we're talking about somewhere between three and five million lives saved every single year. So yes, a huge impact. And if you look at it in the context of individual diseases, we have smallpox, which was a terrible pandemic that went on for centuries and wiped out millions and millions of people.

And that is a virus that's been completely eradicated from the planet. If we think about measles – which, when I started in paediatrics, was killing a million children every year – the global rollout of vaccines over that 35-year period, which is still not reaching everyone, has reduced measles mortality globally by about 90%. The impact is just mind-blowing.

When I started out in paediatrics in the early 1990s, there were diseases I saw regularly then that my trainees here in Oxford today just do not see at all. I find that incredibly invigorating and exciting – to have been involved in vaccination over that period of time, which has essentially erased the experience of junior doctors encountering those diseases.

Chris – How do vaccines actually work, though? What’s the simple kind of mechanism by which what Edward Jenner did a few hundred years ago translates into protection from an infectious disease?

Andrew – Well, essentially, whether you're Edward Jenner or using the latest generation of RNA vaccines developed during the pandemic, they’re all doing the same thing – training our immune system to recognise things which are foreign on the surface of bacteria and viruses, but doing so in a safe way. So you give either part of a virus or you train the cells in our body to make parts of a virus or a bacterium, so that our immune system can be educated. Then, when we actually meet the real bug in the wild, the immune system already knows what to do and gets rid of it, rather than meeting it for the first time, allowing the infection to take hold in our bodies, cause disease, and kill children before the immune system has had time to be educated.

Chris – They fall into different categories, though, vaccines, don’t they? In some cases, we actually give live vaccines. In other cases, we give killed vaccines. In other cases, we give bits of the infectious entity that’s been busted apart, chemically brutalised. In other cases, we give toxins that they make. So what determines what we use and how it works?

Andrew – Some of it is because we knew the mechanisms of the disease were related to particular components. You mentioned the toxins. One great example is tetanus toxoid, which is one of the vaccines we give routinely in five doses throughout childhood.
Tetanus is a bug found in soil that releases a toxin after it gets into wounds in the skin, which can cause paralysis. It’s just by making an immune response against the toxin that we’re able to stop the disease. We’re not fighting the bug.

For other viruses, we know that you can just take one part of the surface of the virus and use that. So the shingles vaccine, which we now use in the UK in the elderly, just has a protein that sits on the surface of the shingles virus, which is the same as the chickenpox virus. And that boosts our immune response so that we’re able to keep shingles at bay.
For other vaccines, people have taken traditional approaches, such as asking, “What if we weaken a virus like measles? Could that then, without causing any significant disease, protect people from measles?” And by trial and error, many vaccines were tested many decades ago to show that this worked.
So in many ways, we choose the type of vaccine partly based on history and partly because of scientific knowledge about which is the right bit of the organism – the bacterium or the virus – to target.