Scientists have moved closer to developing a universal flu vaccine after using the 2009 pandemic as a natural experiment to study why some people seem to resist severe illness.
Researchers at Imperial College London asked volunteers to donate blood samples just as the swine flu pandemic was getting underway and report any symptoms they experienced over the next two flu seasons.
They found that those who avoided severe illness had more CD8 T cells, a type of virus-killing immune cell, in their blood at the start of the pandemic.
They believe a vaccine that stimulates the body to produce more of these cells could be effective at preventing flu viruses, including new strains that cross into humans from birds and pigs, from causing serious disease.
The findings are published in Nature Medicine.
Professor Ajit Lalvani from the National Heart and Lung Institute at Imperial College London, who led the study, said: "New strains of flu are continuously emerging, some of which are deadly, and so the Holy Grail is to create a universal vaccine that would be effective against all strains of flu."
Today's flu vaccines make the immune system produce antibodies that recognise structures on the surface of the virus to prevent infection with the most prevalent circulating strains. But they are usually one step behind as they have to be changed each year as new viruses with different surface structures evolve.
Previously, experimental models had suggested that T cells may protect against flu symptoms but until now this idea has not been tested in humans during a pandemic.
Professor Lalvani's team rapidly recruited 342 staff and students at Imperial to take part in their study in autumn 2009. The volunteers donated blood samples and were given nasal swabs. They were sent emails every three weeks asking them to fill in a survey about their health. If they experienced flu symptoms, they took a nasal swab and sent it back to the lab.
They found that those who fell more severely ill with flu had fewer CD8 T cells in their blood, and those who caught flu but had no symptoms or only mild symptoms had more of these cells.
Professor Lalvani said, "The immune system produces these CD8 T cells in response to usual seasonal flu. Unlike antibodies, they target the core of the virus, which doesn't change, even in new pandemic strains. The 2009 pandemic provided a unique natural experiment to test whether T cells could recognise, and protect us against, new strains that we haven't encountered before and to which we lack antibodies.
"Our findings suggest that by making the body produce more of this specific type of CD8 T cell, you can protect people against symptomatic illness. This provides the blueprint for developing a universal flu vaccine.
"We already know how to stimulate the immune system to make CD8 T cells by vaccination. Now that we know these T cells may protect, we can design a vaccine to prevent people getting symptoms and transmitting infection to others. This could curb seasonal flu annually and protect people against future pandemics."
Professor Lalvani is a Wellcome Trust Senior Research Fellow in Clinical Science and a National Institute for Health Research Senior Investigator. Other members of the team received support from Imperial College Healthcare NHS Trust, the Medical Research Council and Public Health England.
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Notes to editors
1. S Sridhar et al. 'Cellular immune correlates of protection against symptomatic pandemic influenza.' Nature Medicine 2013.
2. About Imperial College London
Consistently rated amongst the world's best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 14,000 students and 6,000 staff of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.
Since its foundation in 1907, Imperial's contributions to society have included the discovery of penicillin, the development of holography and the foundations of fibre optics. This commitment to the application of research for the benefit of all continues today, with current focuses including interdisciplinary collaborations to improve global health, tackle climate change, develop sustainable sources of energy and address security challenges.
In 2007, Imperial College London and Imperial College Healthcare NHS Trust formed the UK's first Academic Health Science Centre. This unique partnership aims to improve the quality of life of patients and populations by taking new discoveries and translating them into new therapies as quickly as possible.
3. About the National Institute for Health Research
The National Institute for Health Research (NIHR) is funded by the Department of Health to improve the health and wealth of the nation through research. Since its establishment in April 2006, the NIHR has transformed research in the NHS. It has increased the volume of applied health research for the benefit of patients and the public, driven faster translation of basic science discoveries into tangible benefits for patients and the economy, and developed and supported the people who conduct and contribute to applied health research. The NIHR plays a key role in the Government's strategy for economic growth, attracting investment by the life-sciences industries through its world-class infrastructure for health research. Together, the NIHR people, programmes, centres of excellence and systems represent the most integrated health research system in the world. For further information, visit the NIHR website.
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