Brainwaves: Catching the flu

Brainwaves: Catching the flu

  • Derek Smith and test tubes

Illustration by Kate Copeland

Professor Derek Smith explains how his research team are working to beat the flu virus at its own game by predicting its evolution.

A radically different approach is to beat the virus at its own game: to predict how it will change, and to vaccinate with a strain from the future. So instead of the virus being one step ahead of us, we are one step ahead of the virus.

One hundred years ago, half of all deaths were caused by infectious disease. Today, that proportion is down to 25 per cent – mostly because of vaccines, antibiotics and improvements in hygiene. Despite this substantial progress, there is a class of pathogens that still cause major problems – those that can change, can evolve, to escape from drugs that used to work and from immunity induced by vaccination or natural infection. Most important among these pathogens is the influenza virus.

About 10 per cent of the world’s population gets flu each year, many millions are hospitalised, and half a million die. Because flu transmits mainly through the air, its spread can’t easily be controlled through hygienic measures. But its most important trick is that it has a seemingly endless capacity to evolve to escape the immunity we get from previous infections, or from vaccines.

One approach to a more permanent protective solution to this virus-on-the-run is the idea of a universal vaccine – a vaccine that targets those parts of the virus that don’t change over time. Though this is a conceptually elegant approach, it remains fraught with challenges, and it remains to be seen if it can be successful.

A radically different approach is to beat the virus at its own game: to predict how it will change, and to vaccinate with a strain from the future. So instead of the virus being one step ahead of us, we are one step ahead of the virus.

Not long ago, most virologists, immunologists and vaccinologists would have said such a prediction was impossible. Nobody understood the evolution well enough, and the possibilities seemed endless. Each time the virus changes, it does so with at least four mutations in 135 possible places (that’s more than a trillion possibilities). Moreover, nobody has ever been able to accurately predict the details of such an evolutionary change in any area, never mind for such an important pathogen.

My research group in Cambridge, together with our close collaborators, the groups of US virologists Ron Fouchier and Yoshi Kawaoka, have been working on figuring out the basic evolutionary processes that govern the evolution of influenza viruses. Over the past 15 years we have made three key discoveries in this area that, when combined, have brought us to a place where predicting what the virus will do next is within reach.

First, we discovered a way to measure flu evolution at a much higher resolution than was previously possible. This allows us to clearly see what is going on, a little like looking down a microscope for the first time and getting to see this previously confusing obscure world clearly. Second, we figured out that of the trillion possibilities of what could be the next type of flu, only about 140 of those possibilities matter. That’s few enough to make and test in the lab, and when we do this we find that the number (to everyone’s surprise) reduces to just one or two because many are equivalent to each other in terms of which is used in a vaccine.

And third, using an extension of the system for seeing the flu evolution at high resolution, we can also see how our immune system is responding with much more clarity than before. We now see that when we are vaccinated or exposed to flu, we don’t only generate immunity against the new strain, but we also boost our immunity against all the older antigenic variants we have seen in the past. We can vaccinate with a ‘future’ strain, to protect against a future virus, and even if we get the prediction wrong, it will be no worse than a traditional vaccine against the current virus.

Can we really make strains of flu in the lab before they exist in nature, and vaccinate people with these strains to protect people against what the virus will do next? Hubris? Perhaps. And this leads me to my favourite quote in all of science by Max Perutz: “In science, truth always wins”. Clinical trials of this new type of vaccine will start in 2019. We will find out.

Derek Smith is Professor of Infectious Disease Informatics in the Department of Zoology. Read more. 

This article first appeared in CAM - the Cambridge Alumni Magazine, edition 80. Find out how to receive CAM.