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Flu vaccine: Babraham Institute researchers uncover potential key to improving immune response in older people



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Scientists at the Babraham Institute hope they have uncovered a key that could help unlock better responses to influenza vaccinations in older people.

We know that our immune response to the flu jab declines as we age, but researchers have so far struggled to explain why.

Dr Michelle Linterman at the Babraham Institute. Picture: Keith Heppell
Dr Michelle Linterman at the Babraham Institute. Picture: Keith Heppell

Dr Michelle Linterman and her team at Babraham looked for answers by comparing more than 50 immune variables in individuals of different ages before and after vaccination.

These included the level of neutralising antibodies raised to the protein the flu virus uses to enter cells - haemagglutinin - along with cell signalling molecules and the responses of B and T cells, which are key components of the immune system.

The researchers tracked the immune cells that respond to the vaccination, so that they were sure the changes were the result of the seasonal flu jab.

The immunologists found that a particular type of white blood cells - circulating T follicular helper cells - were linked with good influenza antibody responses in younger people.

However, in those aged over 65, the formation of these cells upon vaccination was reduced by comparison.

The immunologists found gene expression differences in these cells from older people, which drive an inflammation response to the vaccination.

That response had a negative impact on the formation ot these circulating T follicular helper cells, which are essential for supporting good antibody production and developing immunity.

The findings, published in eLife, suggest that a strategy of limiting this negative pro-inflammatory signalling could improve the efficacy of the vaccine, particularly for older people.

Dr Michelle Linterman at the Babraham Institute. Picture: Keith Heppell
Dr Michelle Linterman at the Babraham Institute. Picture: Keith Heppell

Dr Linterman said: “Understanding the molecular events behind our body's response to vaccination shows us what is happening when the immune response isn't as strong as it could be.

“Our research provides a proof of concept that enhanced inflammation is a feature of the vaccination response in older people and that this limits the formation of T follicular helper cells, which are in turn essential for supporting good antibody production.

“This suggests that strategies that temporarily dampen inflammation at the time of vaccination may be a viable strategy to boost optimal antibody generation upon immunisation of older people.”

The research explains that the number of circulating T follicular helper cells (cTfh) that specifically recognise the influenza protein haemagglutinin were the best indicator for a strong immune response.

These cells differentiate from pre-existing ‘memory cells’, but in older people this differentiation process is reduced.

Seeking the reasons for this impaired cTfh cell differentiation in older people, the researchers looked to the transcriptome. This is the collection of gene read-outs, or transcripts, created when DNA instructions are ‘read’ and copied in RNA.

They aimed to detect the differences in the genes expressed in the vaccine-specific cTfh cells from younger and older individuals.

Dr Michelle Linterman at the Babraham Institute. Picture: Keith Heppell
Dr Michelle Linterman at the Babraham Institute. Picture: Keith Heppell

They found that cells from older individuals failed to acquire the full gene signature seen in Tfh cells from younger people.

They also discovered pro-inflammatory signalling pathways in cTfh cells were activated in older people in response to vaccination, which negatively impacted the vaccine response.

In England and Wales, 1,596 died from flu in 2018, and 1,213 died from it in 2019.

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