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Flu Vaccines

24 - 30 April 2014 marks World Health Organisation (WHO) World Immunization Week; this year’s theme is ‘Immunize for a healthy future: Know. Check. Protect’. 

NDM spoke to Professor Sarah Gilbert, Professor of Vaccinology and Programme leader in Human Influenza Vaccines at the Jenner Institute, about her research developing a ‘universal flu vaccine’ and the importance of vaccinating against flu.

Sarah GilbertQ: Who should be vaccinated against flu and why do they need to be vaccinated every year?

Sarah Gilbert: Anyone who is at risk of becoming severely ill if they are infected by the influenza virus should be vaccinated. That includes everyone over the age of 65, pregnant women, people with weakened immune systems and people with chronic health conditions such as asthma, heart failure or chronic kidney disease. There is also a new vaccine that works very well in children, given by nasal spray, and is now being given to two and three year olds in the UK.

There are two reasons for getting vaccinated each year. The flu vaccine changes slightly each year. That happens because the flu viruses that are causing disease in people are changing slightly all the time. Our immune system makes antibodies to parts of the virus surface, especially a protein called haemagglutinin (HA for short). The vaccine needs to have the same version of HA as the most recent viruses that are causing flu, so that our immune system receives the instructions to make the right antibodies. If we carried on using the same vaccine we’d be making antibodies to a virus that used to give people flu, not the one that is doing so this year, so that vaccine is continually updated. The other reason is that the effects of the vaccine don’t last for very long. Occasionally there is a lot of flu around very late in the season, and in those years vaccinated people aren’t protected as well as they usually are. So even if you had your flu vaccine last year, you need to have it again at the start of the next flu season.

'Flu Jab' by NHS Employers via Flickr. Used under a Creative Commons 2.0 License.'Flu Jab' by NHS Employers via Flickr. Used under a Creative Commons 2.0 License.Q: Why is the current flu vaccine less effective in older adults?

SG: As with many things, the immune system stops working as well when we get older.

It doesn’t suddenly give up completely, but older adults don’t make antibodies to HA after vaccination as efficiently in younger people. However it’s still worth having the vaccine, as if you do get infected, the disease won’t be as severe as if you hadn’t been vaccinated. Influenza can be a really serious disease in older people, and this is the age group that is most at risk of death from influenza.

Now that the new vaccine is starting to be used in children in the UK, we might see that this has a beneficial effect for older people as well as the children. When young children are infected with influenza they may not get very ill, but tend to produce very large amounts of virus that they generously share with anyone who comes into contact with them. If these children are protected by vaccination, not only will they not get ill but there will be less virus being passed on to grandparents. In future more children will get the vaccine and that might start to make a difference to older people getting flu as well.

Q: What is a ‘universal flu vaccine’ and how does it work?

SG: In principle a universal flu vaccine is a vaccine that works against any strain of flu, whether it’s one that has been circulating among humans and gradually changing over time, or a very different ‘pandemic’ virus that moves from birds or pigs into humans. In practice, there is no such thing, it’s just an idea, but one that people like me are trying to turn into reality.

The problem with concentrating on HA in the vaccine is that there are so many different versions of HA that are possible so a new vaccine has to be made for each strain of the virus. That poses a real problem in the event of a pandemic since we can’t make a vaccine until we know exactly what the HA in the pandemic virus is. If we want a vaccine to stimulate an immune response that will protect against any flu virus, that immune response will have to recognise some part of the virus that doesn’t keep changing. But most of the outside of the virus is covered with proteins that do keep changing. There are other proteins inside the virus that change very little, but antibodies can’t reach inside the virus to get to them. So the approach of my research team is to stimulate a different part of the immune system - the T cells. T cells recognising these conserved internal proteins are a really important part of the natural immune response to influenza. They can recognise cells in our airways that are infected with flu virus and kill them before the virus can spread and make the infection worse. If there are enough of them around when we get a flu virus infection, the T cells can kill the first few cells that are infected and nip the disease in the bud so quickly that we don’t even realise we’ve been infected - as so-called asymptomatic infection.

The vaccine that we are working on boosts T cell responses that recognise two of the conserved proteins inside the influenza virus. We’ve done clinical trials using it on its own, and also giving it with the existing flu vaccine. We’ve seen really promising results using both vaccines together so far, and this might be a way of making a vaccine that works much better in older people. We’re now hoping to do a study in people aged over 65 years in which half of them will get the usual vaccine and half of them will get the new vaccine as well. Then they will keep a diary of their influenza like illnesses for that winter, as well as providing blood samples for lab tests, and we’ll be able to find out if the ones who get both vaccines have less flu. If they do, then we’re on the right track but there will still be more trials to do before the vaccine will become generally available.

Other research groups are taking different approaches, for example concentrating on small regions on the outside of the virus that don’t change much, and might be reached by antibodies. However we don’t yet know if it will be possible to make a vaccine that stimulates antibodies to those regions. So there’s still a long way to go, and once we know how to make a vaccine that protects against all flu strains, we will still have to work out how often it needs to be given. In the meantime, if you’re invited to receive your flu vaccine, don’t ignore the invitation!