Influenza A virus is a highly contagious respiratory infection that can cause a host of unpleasant symptoms and even death in some. Influenza can be particularly serious for the elderly and those with chronic heart and lung diseases, who are at higher risk of becoming more severely ill. Vaccines against influenza currently exist, but in order to make these scientists have to predict in advance which strain they think will be circulating the following year. As influenza virus can mutate and change in the time it takes to manufacture a vaccine, vaccination often fails to protect people against a newly mutated versions of a virus. An additional problem is that even when scientists correctly predict a viral strain, the vaccine may still be poor at generating immune responses to the virus. It is therefore important to develop new and improved vaccines that provide broader protection against a wide range of influenza viruses.
One approach to tackle these problems is improving our understanding of how the body’s immune system recognises and responds to the flu virus. I hope to do this by deciphering the information which is transferred by tiny information pods called exosomes, released by almost all cells in the body. Exosomes are nano-sized cell shuttles that communicate important information from cell to cell. We know that their messages can be altered during infection, and possibly when responding to vaccination. Because of this, there is great potential to manipulate their interactions with the cells of the immune system to improve vaccine responses.
My research aims to study exosome communication in two ways. One approach is to better understand what is contained in exosomes following vaccination. In other words, what are the messages being transferred from cell to cell and how do they affect the immune response? Another approach is to exploit the cell:cell transfer properties of exosomes and hijack these shuttles by designing vaccines which can artificially deliver fragments of the influenza virus (called proteins) to exosomes. Through doing this we hope that more immune cells will recognise influenza proteins and become activated, dramatically improving the body’s immune response and providing greater protection. We are particularly interested in using fragments of the influenza virus which do not mutate so that these "universal influenza vaccines" could generate immune responses capable of protecting against a diverse range of strains.
The HC Roscoe grant from the BMA foundation has allowed me to pursue this research project and to establish a collaboration between the Jenner Institute, University of Oxford and Icahn School of Medicine at Mount Sinai, New York, where I am currently working within Prof Peter Palese's world renowned influenza virology laboratory. The in-house expertise and complementary approaches to generating universal influenza vaccines at Mount Sinai ensure that this study will lead to the design of more effective influenza vaccines for clinical investigation and pandemic preparedness, with the potential to beneficially impact patient health, society and the economy.