Vaccinations: a Global Challenge

The Institute’s research is having a major impact on global public health. Although the first vaccines were developed more than two centuries ago, infectious diseases such as malaria and influenza still affect millions of people each year. By improving our understanding of the immune system and its response to modern vaccines, the Institute is paving the way for better vaccines that will protect more people from life-threatening diseases.

 

When it comes to human health, our immune system is our most important defence against illness and disease. Producing antibodies is one of the ways that the immune system counteracts pathogens – the causes of illness. Yet, this system is not perfect. Sometimes the body produces antibodies against the wrong things – resulting in allergies, autoimmune diseases and organ rejection – while at other times it fails to produce enough antibodies to fight infections including malaria and influenza. And as we age, our immune system becomes less adept at combatting infection and responding to vaccination.



As well as being extraordinarily powerful, our immune system is amazingly complex and continues to pose significant scientific challenges. Key among these is how to design ‘flu vaccines that are more effective in an ageing population, and how to boost the efficacy of vaccines to prevent malaria. Dr Michelle Linterman, a Group Leader in the Institute’s Immunology research programme, is making important advances in both.



“One of our major goals is to improve vaccine efficacy as we age. The seasonal ‘flu vaccine provides 80% protection against infection if you’re aged between 18 and 60. Over the age of 60 vaccine efficacy decreases – and for people over 70 it’s only 25% effective,” she explains. “This does not mean that older people shouldn’t get vaccinated, because complications associated with ‘flu can be very serious. But it does mean there’s an opportunity to improve the way these vaccines work for older persons.”



Part of the problem arises from how clinical trials have traditionally been run. Almost all immunology research – including vaccine trials – is done in young animals and people; what’s lacking is research in the populations that vaccines most need to protect. This is true not only of ‘flu but in malaria too. Most malaria vaccine trials are run in European populations, and success here often fails to translate to those in most need – the people who live in malaria-endemic areas.



Most vaccines provide protection against infection via production of antibodies, the proteins our immune cells secrete. In ‘flu, for example, these antibodies bind to the virus and prevent it from infecting our cells. At the same time, antibodies signal to other immune cells to destroy the virus. Our immune systems are very diverse, which helps to protect us from pandemics, but complicates vaccination programmes as individual responses to vaccines are very variable.

What’s needed is more cleverly-designed trials, which is exactly what Michelle and her team are doing in both Cambridge and East Africa. To design better ‘flu studies, she’s using the Cambridge Bioresource, a unique panel of 17,000 volunteers willing to take part in research and who have already donated DNA. “The Cambridge Bioresource is a phenomenal research resource; it allows us to design much smarter studies because we can select people with particular genotypes and recruit people to studies much more quickly than before.”



These studies are revealing why older people produce fewer antibodies after ‘flu vaccination, opening up new ways of making vaccines more effective. “We’ve run two studies showing that the T cell response is impaired,” she says. “And now we know where the cellular defect lies, it should be possible to change the adjuvants – the ingredients in vaccines that stimulate the immune system – to boost these T cells.”



Thanks to support from the Global Challenges Research Fund, Michelle is working on large-scale collaborative vaccine trials in malaria-endemic Tanzania and Mozambique. Her aim is to understand – in immunological terms – why people respond so differently to existing malaria vaccines, and discover whether new adjuvants could make malaria vaccines more effective. After analysing samples from children vaccinated with RTS,S (which is the best malaria vaccine on the market but one with plenty of room for improvement), the team uncovered important differences in the immune cells of children who respond well to the vaccine compared with those who do not. They also made new discoveries in the adjuvant trials.



“We’ve just finished a study in young Africans that clearly shows that a new adjuvant does a good job of boosting T cells,” she concludes. “Being involved in trials of new adjuvants is very exciting. Our research shows that these adjuvants could help boost the T cell response after vaccination in older people, and it illustrates that our fundamental science is crucial to delivering better vaccines across the world.”



This feature was written by Becky Allen for the Annual Research Report 2017