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Hopes for more effective flu vaccine after Babraham Institute discovery


By Paul Brackley


Each year a new influenza vaccine is produced, based on the World Health Organization’s insights into the prevailing strains.

Dr Alice Denton in the imaging facility at the Babraham Institute. Picture: Babraham Institute (7776157)
Dr Alice Denton in the imaging facility at the Babraham Institute. Picture: Babraham Institute (7776157)

It is vital – and prevents millions of infections and tens of thousands of death – but its effectiveness varies from year to year as the virus is not easy to predict.

Now immunology researchers at the Babraham Institute have made a discovery about how lung tissue responds to an influenza infection, which could help vaccine manufacturers deliver more robust protection in future.

Studying the impact of flu in mice, they found that the body remodels its lung tissue to support an immune system response.

A key effect of this remodelling is the production of antibodies that have the ability to provide protection against a wider range of related viruses.

Dr Alice Denton, BBSRC future leader fellow at the Babraham Institute, said: “In the same way that crisis centres are created on the ground in the midst of a humanitarian effort, the immune system can commandeer non-immune-related tissues to create something that resembles an immune cell hub where white blood cells collaborate to generate a co-ordinated response to an invading pathogen.”

These transient microenvironments are called germinal centres.

Mouse lung (in blue) 14 days after influenza A infection with ectopic lymphoid structures identified by the presence of high numbers of B cells (in green) and T cells (in pink). Microscopy: Dr Alice Denton, Babraham Institute (7776142)
Mouse lung (in blue) 14 days after influenza A infection with ectopic lymphoid structures identified by the presence of high numbers of B cells (in green) and T cells (in pink). Microscopy: Dr Alice Denton, Babraham Institute (7776142)

They are critical for generating an effective immune response and awakening our immune ‘memory’, which provides protection against subsequent infections.

But how they are formed in the lungs after infection has been a mystery.

The Babraham researchers found a cascade of events is responsible for initiating the formation.

A chemical message, known as type 1 interferon, is produced by lung cells in response to infection. This triggers the production of a chemical attractant, which effectively calls in the immune system.

The signal recruits antibody-producing B cells to the lungs, initiating the formation of germinal centres.

Dr Alice Denton in the imaging facility at the Babraham Institute. Picture: Babraham Institute (7776160)
Dr Alice Denton in the imaging facility at the Babraham Institute. Picture: Babraham Institute (7776160)

These centres produce a different repertoire of B cells, that provide antibodies that are more broadly reactive against different influenza strains.

Reporting their findings in the Journal of Experimental Medicine, the researchers suggest that understanding the compounds that stimulate a type I interferon response may be useful as vaccine additions.

Dr Michelle Linterman, research group leader at the Babraham Institute, said: “One important function of germinal centres when responding to infection is that they support the creation of cross-reactive antibodies that can confer wider protection.

“Being able to exploit this would be extremely beneficial in the case of the annual influenza vaccination where the vaccination is developed against the likely prevalent strain. In the case of vaccinating against one type of influenza virus, wider protection against other types of influenza strains would reduce infections and thereby improve health.”

Dr Alice Denton in the imaging facility at the Babraham Institute. Picture: Babraham Institute (7776145)
Dr Alice Denton in the imaging facility at the Babraham Institute. Picture: Babraham Institute (7776145)

In the severe 2017-18 flu season, the annual vaccine reduced the risk of getting the virus among those who had it by just 15 per cent, according to Public Health England, although it varied considerably among age groups. It was more effective in children, and provided particularly good protection against two strains.

In 2018-19, a booster vaccine was made available to over-65s and the quadrivalent vaccine given to children, which protects against four strains instead of three, was recommended for at-risk adults.

Applying the findings of the Babraham research could help improve the creation of the annual vaccine.

The research findings are also significant in understanding immune responses in non-lymphoid tissues, known to be associated with autoimmune disease, infection, chronic obstructive pulmonary disease and cancer.

Dr Denton said: “Understanding how these ectopic immune structures form may enable the development of new therapeutics to specifically target these responses. In autoimmune disease, this has the potential to reduce the detrimental immune responses that are targeted against the body’s own tissue.”

Dr Alice Denton in the imaging facility at the Babraham Institute. Picture: Babraham Institute (7776148)
Dr Alice Denton in the imaging facility at the Babraham Institute. Picture: Babraham Institute (7776148)


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