Researchers from the University of Oxford’s Department of Zoology have demonstrated pre-clinical success for a universal flu vaccine.
Seasonal influenza is estimated to cause between 1 and 4 million cases of severe illness and 200,000 to 500,000 deaths per year1. The best way to protect against influenza infection is through vaccination. Currently, a trivalent (TIV) or quadravalent influenza (QIV) vaccine is given each year, targeting the circulating H1N1 and H3N2 influenza A strains and one or two lineages of the circulating influenza B strains. However, the vaccine has to be formulated at least 6 months prior to the influenza season and so the strains that are subsequently prevalent in the actual flu season do not always match the strains used in the vaccine.
Influenza is thought to be a highly variable virus, able to mutate and escape immunity built up in the population due to its circulation in previous seasons. However, influenza seasons tend to be dominated by a limited number of antigenically and genetically distinct influenza viruses. This creates a paradox as influenza is thought of as being highly variable while in reality influenza seasons are dominated by only a few strains.
Mathematical models produced in Professor Sunetra Gupta’s group at the University of Oxford over the past 20 years have sought to find an answer to this paradox. Finally, through a collaborative approach across multiple departments, the group believes they have the answer.
Results were explained in a paper in Nature Communications.
The research team theorized that parts of the virus targeted by the immune system are, in fact, limited in variability and act as constraints on the evolution of the virus. Dr Craig Thompson in Professor Gupta’s group has now identified the location of these regions of limited variability. He has shown that such locations are targeted naturally by the immune system and through vaccination studies has shown that regions of influenza viruses that circulated in 2006 and 1977 were able to protect against infection with an influenza virus that last circulated in 1934.
The results of these studies can be exploited to create a novel type of ‘universal’ or broadly protective influenza vaccine, which once administered would provide lifelong protection against influenza. The team also hopes to apply the approach to other viruses such as HIV and HCV and believes that they can use it to produce a vaccine that protects against the common cold.
This study also presents one of the first examples of where a mathematical model of the evolutionary dynamics of an infectious disease has led to the experimental identification of a novel vaccine target.
I think this work serves a good example of how evolutionary models can have translational impact. We have gone from a prediction of a mathematical model to a blueprint for a universal influenza vaccine. The outstanding teamwork coordinated by Dr Thompson is what made it all possible", professor Sunetra Gupta said.