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Monday, 24 October 2016

Time for T? The role of T cells in influenza vaccination.

It is approaching flu season again. If you are in any way susceptible to flu – over 65, have an underlying health condition (asthma, MS, pregnancy) get the flu vaccine (I have nagged my parents already – but Mum, Dad if you are reading this don’t forget). The current flu vaccine works well and will protect you against this year’s flu.

See my coat of many, many colours

But we could do better. Vaccines work by training your body to recognise the coat that surrounds the flu virus. The big problem is that flu mutates, changing its coat, hiding from our immune system. The gene machinery encoded by the influenza virus is inefficient (leaky). Imagine using a photocopier to make repeat copies of the same document each time using the copy as the template for the next round; over time the quality of the copies declines. DNA is copied in the same way with faults in the copies leading to errors in genes (mutations), most of which are harmless, some harmful and some beneficial – this is the driving engine of evolution. Eukaryotic cells (us) have proofreading in the gene copying machinery, if a faulty copy is made it is deleted, viruses do not have this, so the chance of a faulty copy increases. This means that viruses can mutate/ change quickly leading to the emergence of new viruses with new coats each year necessitating new vaccines.

Killer cells

A goal of influenza research is to develop vaccines that cover a wider spectrum of viruses – the universal flu vaccine. But to achieve this goal, we need to understand more about the way in which the body fights off flu infection. This is what we set out to do in our recently published paper: “DNA Vaccines Encoding Antigen Targeted to MHC Class II Induce Influenza-Specific CD8+ T Cell Responses, Enabling Faster Resolution of Influenza Disease”. Using unique vaccines from our Norwegian collaborators, Vaccibody, we dissected one aspect of the immune response called the CD8 T cell. These cells are able to sense when other cells have viruses in them and then kill the infected cells. The vaccines are designed to target different types of cells and can be used to alter the flavour of the immune response. Using a CD8 T cells specific Vaccibody, we showed was that vaccines that evoke a T cell response led to a faster resolution of disease – infected animals got better, quicker. This is important because the influenza virus may be less good at escaping CD8 T cells than other parts of the immune response. Based on these studies, we believe that the next generation of influenza vaccines need to increase the CD8 T cell response. This idea is supported by research performed during the influenza pandemic in 2009: patients who had a functional CD8 response were much less likely to get sick after infection. The more we understand about the immune response, the better vaccines get and the less people will  get sick from infections.