A team of researchers from the University of Southampton, University of Oxford and Retroscreeen Virology Ltd have discovered a series of peptides, found on the internal structures of influenza viruses that could lead to the development of a universal vaccine for influenza, one that gives people immunity against all strains of the disease, including seasonal, avian, and swine flu.
Influenza, an acute viral infection, affects hundreds of thousands of people a year and puts an enormous strain on healthcare providers globally. The last pandemic flu outbreak in the UK — swine flu — was in 2009 when it claimed 457 lives. While previous pandemics have been more serious, there is a heightened risk of more severe pandemics in the future.
The scientific collaboration used a research method known as Human Viral Challenge Studies, where healthy volunteers are infected with influenza virus, and their immune responses closely monitored in an isolation unit.
These were important to the research, as they allowed the healthy volunteers to be held in “sterile” isolation conditions and ensured they had no existing infections. The volunteers were then “challenged” with influenza virus, with blood samples being taken at regular intervals to observe how their immune systems responded to the viral infection.
Internal Virus Structures
Researchers discovered that the immune systems produced various types of T-cells (part of the immune system that kills both viral particles, and cells infected with viral particles). Notably, the T-cells responded to peptides associated with the internal structures of the influenza viruses.
Unlike the external structures of influenza virus, that mutates very rapidly and creates a new strain of virus most years, the internal structures change very slowly over a long period of time. These internal structures are found in all strains of influenza virus.
Thus, a vaccine that targets such peptides may provide immunity against all strains of influenza, including seasonal (yearly), avian (bird), and swine flu, for many years.
A vaccine against these peptides would activate the T-cell immune response — which is able to respond much more rapidly than vaccines that activate an antibody response.
Dr Tom Wilkinson, Senior Lecturer in Respiratory Medicine at the University of Southampton, who led the study, says:
“Influenza is a virus that we know has a global impact, and the threat of further pandemics is a real one. Most influenza vaccines only protect us against known influenza strains by creating antibodies in the blood but the influenza virus has the ability to rapidly change itself and new strains can emerge which rapidly spread across the globe by escaping this immunity.
We have found that there is an important role for T-cells that recognise the flu virus, which if harnessed could protect against most or even all strains of seasonal and pandemic flu. Through this discovery we hope to improve vaccines for future strains of influenza; and potentially protect against the next pandemic. However there is more to do to translate these findings into new approaches to treatment.”
Adds Professor Sir Andrew McMichael, Director of the Medical Research Council (MRC) Weatherall Institute of Molecular Medicine at Oxford University:
“Current flu vaccines are very good at producing antibodies against flu, but not so good at generating a lasting immunity involving T-cells. The big question is: if we had a pandemic involving a much more severe virus than the swine flu we saw, what would we do in the six months it takes to develop an effective vaccine?
This study suggests that vaccines stimulating a T-cell response might be an option, but there remains a lot to do to be certain of this approach.”
Tom M Wilkinson, Chris K F Li, Cecilia S C Chui, Arthur K Y Huang, Molly Perkins, Julia C Liebner, Rob Lambkin-Williams, Anthony Gilbert, John Oxford, Ben Nicholas, Karl J Staples, Tao Dong, Daniel C Douek, Andrew J McMichael, Xiao-Ning Xu
Preexisting influenza-specific CD4 T cells correlate with disease protection against influenza challenge in humans
Nature Medicine, 2012; DOI: 10.1038/nm.2612
Illustration: U.S. Centers for Disease Control and Prevention